NM_003742.4(ABCB11):c.2343+1G>T AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Aug 2, 2023
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:: RCV001039189.10

Allele description [Variation Report for NM_003742.4(ABCB11):c.2343+1G>T]

NM_003742.4(ABCB11):c.2343+1G>T

Gene:

ABCB11:ATP binding cassette subfamily B member 11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.1

Genomic location:

Preferred name:

NM_003742.4(ABCB11):c.2343+1G>T

HGVS:

NC_000002.12:g.168957963C>A
NG_007374.2:g.78434G>T
NM_003742.4:c.2343+1G>TMANE SELECT
LRG_1199t1:c.2343+1G>T
LRG_1199:g.78434G>T
NC_000002.11:g.169814473C>A
NM_003742.2:c.2343+1G>T

Links:

dbSNP: rs774411820

NCBI 1000 Genomes Browser:

rs774411820

Molecular consequence:

NM_003742.4:c.2343+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001202705	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 2, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 18395098, 20232290, 16871584, 24991443, 28492532
SCV001812441	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Dec 31, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001202705

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 2, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

SCV001812441

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Dec 31, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families.

Strautnieks SS, Byrne JA, Pawlikowska L, Cebecauerová D, Rayner A, Dutton L, Meier Y, Antoniou A, Stieger B, Arnell H, Ozçay F, Al-Hussaini HF, Bassas AF, Verkade HJ, Fischler B, Németh A, Kotalová R, Shneider BL, Cielecka-Kuszyk J, McClean P, Whitington PF, Sokal E, et al.

Gastroenterology. 2008 Apr;134(4):1203-14. doi: 10.1053/j.gastro.2008.01.038. Epub 2008 Jan 18.

PubMed [citation]

PMID:: 18395098

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001202705.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change affects a donor splice site in intron 19 of the ABCB11 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ABCB11 are known to be pathogenic (PMID: 18395098, 20232290). This variant is not present in population databases (gnomAD no frequency). 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 disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 837780). Disruption of this splice site has been observed in individuals with clinical features of progressive familial intrahepatic cholestasis (PMID: 16871584, 24991443).

#	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 GeneDx, SCV001812441.1

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

Description

Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown; Observed with a pathogenic variant in individuals with progressive familial intrahepatic cholestasis in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in some cases (Scheimann et al., 2007; Strautnieks et al., 2008); Observed in the heterozygous state in a female with intrahepatic cholestasis of pregnancy (Dixon et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26689913, 18395098, 28924228, 17452236, 25525159, 24991443)

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

Last Updated: Oct 13, 2024

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