NM_003742.4(ABCB11):c.677C>T (p.Ser226Leu) AND Progressive familial intrahepatic cholestasis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 2023
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:: RCV003401948.1

Allele description [Variation Report for NM_003742.4(ABCB11):c.677C>T (p.Ser226Leu)]

NM_003742.4(ABCB11):c.677C>T (p.Ser226Leu)

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.677C>T (p.Ser226Leu)

Other names:

NM_003742.4(ABCB11):c.677C>T; p.Ser226Leu

HGVS:

NC_000002.12:g.168993817G>A
NG_007374.2:g.42580C>T
NM_003742.4:c.677C>TMANE SELECT
NP_003733.2:p.Ser226Leu
LRG_1199t1:c.677C>T
LRG_1199:g.42580C>T
LRG_1199p1:p.Ser226Leu
NC_000002.11:g.169850327G>A
NM_003742.2:c.677C>T

Protein change:

S226L

Links:

dbSNP: rs1382100120

NCBI 1000 Genomes Browser:

rs1382100120

Molecular consequence:

NM_003742.4:c.677C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Progressive familial intrahepatic cholestasis (PFIC)
Synonyms:: Progressive intrahepatic cholestasis; Progressive family intrahepatic cholestasis
Identifiers:: MONDO: MONDO:0015762; MedGen: C0268312; OMIM: PS211600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004122504	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Oct 4, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32808743, 20232290, 20414253 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004122504

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Oct 4, 2023)

germline

clinical testing

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

Citation Link

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

ABCB11 deficiency presenting as transient neonatal cholestasis: Correlation with genotypes and BSEP expression.

Li LT, Li ZD, Yang Y, Lu Y, Xie XB, Chen L, Feng JY, Knisely AS, Wang JS.

Liver Int. 2020 Nov;40(11):2788-2796. doi: 10.1111/liv.14642. Epub 2020 Oct 13.

PubMed [citation]

PMID:: 32808743

ATP8B1 and ABCB11 analysis in 62 children with normal gamma-glutamyl transferase progressive familial intrahepatic cholestasis (PFIC): phenotypic differences between PFIC1 and PFIC2 and natural history.

Davit-Spraul A, Fabre M, Branchereau S, Baussan C, Gonzales E, Stieger B, Bernard O, Jacquemin E.

Hepatology. 2010 May;51(5):1645-55. doi: 10.1002/hep.23539.

PubMed [citation]

PMID:: 20232290

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004122504.1

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

Description

Variant summary: ABCB11 c.677C>T (p.Ser226Leu) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain (IPR011527) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 246750 control chromosomes (gnomAD). c.677C>T has been reported in the literature in multiple individuals affected with Familial Intrahepatic Cholestasis (Davit-Spraul_2010, Shapiro_2010, Li_2020). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 20232290, 20414253, 32808743). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as pathogenic/likely pathogenic (n=2) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as 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

Last Updated: Apr 20, 2025

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