NM_000414.4(HSD17B4):c.1768-1G>A AND Bifunctional peroxisomal enzyme deficiency

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Mar 23, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003155657.3

Allele description [Variation Report for NM_000414.4(HSD17B4):c.1768-1G>A]

NM_000414.4(HSD17B4):c.1768-1G>A

Gene:

HSD17B4:hydroxysteroid 17-beta dehydrogenase 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q23.1

Genomic location:

Preferred name:

NM_000414.4(HSD17B4):c.1768-1G>A

HGVS:

NC_000005.10:g.119529893G>A
NG_008182.1:g.82441G>A
NM_000414.4:c.1768-1G>AMANE SELECT
NM_001199291.3:c.1843-1G>A
NM_001199292.2:c.1714-1G>A
NM_001292027.2:c.1696-1G>A
NM_001292028.2:c.1348-1G>A
NM_001374497.1:c.1759-1G>A
NM_001374498.1:c.1696-1G>A
NM_001374499.1:c.1441-1G>A
NM_001374500.1:c.1327-1G>A
NM_001374501.1:c.1357-1G>A
NM_001374502.1:c.1357-1G>A
NM_001374503.1:c.1357-1G>A
NC_000005.9:g.118865588G>A
NM_000414.3:c.1768-1G>A

Links:

dbSNP: rs1359482508

NCBI 1000 Genomes Browser:

rs1359482508

Molecular consequence:

NM_000414.4:c.1768-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001199291.3:c.1843-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001199292.2:c.1714-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001292027.2:c.1696-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001292028.2:c.1348-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001374497.1:c.1759-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001374498.1:c.1696-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001374499.1:c.1441-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001374500.1:c.1327-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001374501.1:c.1357-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001374502.1:c.1357-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001374503.1:c.1357-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Bifunctional peroxisomal enzyme deficiency (DBIF)
Synonyms:: DBP DEFICIENCY; PBFE DEFICIENCY; D-bifunctional protein deficiency
Identifiers:: MONDO: MONDO:0009855; MedGen: C0342870; OMIM: 261515

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003844413	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Feb 7, 2023)	germline	clinical testing	Citation Link,
SCV004192394	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 23, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003844413

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Feb 7, 2023)

germline

clinical testing

Citation Link,

SCV004192394

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 23, 2024)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844413.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: HSD17B4 c.1768-1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250100 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1768-1G>A in individuals affected with D-Bifunctional Protein Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004192394.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine