NM_000443.4(ABCB4):c.3370dup (p.Cys1124fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 13, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003083388.2

Allele description [Variation Report for NM_000443.4(ABCB4):c.3370dup (p.Cys1124fs)]

NM_000443.4(ABCB4):c.3370dup (p.Cys1124fs)

Gene:

ABCB4:ATP binding cassette subfamily B member 4 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

7q21.12

Genomic location:

Preferred name:

NM_000443.4(ABCB4):c.3370dup (p.Cys1124fs)

HGVS:

NC_000007.14:g.87406404dup
NG_007118.3:g.74623dup
NM_000443.3:c.3370dupT
NM_000443.4:c.3370dupMANE SELECT
NM_018849.3:c.3391dup
NM_018850.3:c.3229dup
NP_000434.1:p.Cys1124fs
NP_061337.1:p.Cys1131fs
NP_061338.1:p.Cys1077fs
NC_000007.13:g.87035719_87035720insA
NC_000007.13:g.87035720dup
NG_007118.2:g.79029dup

Protein change:

C1077fs

Molecular consequence:

NM_000443.4:c.3370dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018849.3:c.3391dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018850.3:c.3229dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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THO complex subunit 4D [Oryza sativa Japonica Group]
THO complex subunit 4D [Oryza sativa Japonica Group]
gi|1002279783|ref|XP_015644210.1|

Protein
SMAD1 SMAD family member 1 [Sus scrofa]
SMAD1 SMAD family member 1 [Sus scrofa]
Gene ID:397016

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003457415	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 13, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17726488, 25755532, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003457415

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 13, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Molecular characterization and structural implications of 25 new ABCB4 mutations in progressive familial intrahepatic cholestasis type 3 (PFIC3).

Degiorgio D, Colombo C, Seia M, Porcaro L, Costantino L, Zazzeron L, Bordo D, Coviello DA.

Eur J Hum Genet. 2007 Dec;15(12):1230-8. Epub 2007 Aug 29.

PubMed [citation]

PMID:: 17726488

Progressive familial intrahepatic cholestasis.

Srivastava A.

J Clin Exp Hepatol. 2014 Mar;4(1):25-36. doi: 10.1016/j.jceh.2013.10.005. Epub 2013 Nov 23. Review.

PubMed [citation]

PMID:: 25755532
PMCID:: PMC4017198

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003457415.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with ABCB4-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.03%). This sequence change creates a premature translational stop signal (p.Cys1124Leufs*20) in the ABCB4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCB4 are known to be pathogenic (PMID: 17726488, 25755532).

#	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

Last Updated: Sep 16, 2024

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