rs2287616

Positions:

chr2-168990902-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003742.4(ABCB11):c.807T>C(p.Tyr269=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,613,022 control chromosomes in the GnomAD database, including 2,081 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 254 hom., cov: 32)

Exomes 𝑓: 0.012 ( 1827 hom. )

Consequence

ABCB11
NM_003742.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.104

Variant links:

Genes affected

ABCB11 (HGNC:42): (ATP binding cassette subfamily B member 11) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is the major canalicular bile salt export pump in man. Mutations in this gene cause a form of progressive familial intrahepatic cholestases which are a group of inherited disorders with severe cholestatic liver disease from early infancy. [provided by RefSeq, Jul 2008]

ABCB11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-168990902-A-G is Benign according to our data. Variant chr2-168990902-A-G is described in ClinVar as [Benign]. Clinvar id is 259157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.104 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB11	NM_003742.4 linkuse as main transcript	c.807T>C	p.Tyr269=	synonymous_variant	9/28	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1 linkuse as main transcript	c.807T>C	p.Tyr269=	synonymous_variant	9/28		NM_003742.4	ENSP00000497931	P1

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2307

AN:

152164

Hom.:

255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0261

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.0327

AC:

8111

AN:

248324

Hom.:

877

AF XY:

0.0282

AC XY:

3797

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.00349

Gnomad AMR exome

AF:

0.0596

Gnomad ASJ exome

AF:

0.00967

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.0103

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.000881

Gnomad OTH exome

AF:

0.0227

GnomAD4 exome

AF:

0.0117

AC:

17110

AN:

1460740

Hom.:

1827

Cov.:

AF XY:

0.0112

AC XY:

8174

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.00191

Gnomad4 AMR exome

AF:

0.0529

Gnomad4 ASJ exome

AF:

0.00935

Gnomad4 EAS exome

AF:

0.283

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.000687

Gnomad4 OTH exome

AF:

0.0241

GnomAD4 genome

AF:

0.0151

AC:

2305

AN:

152282

Hom.:

254

Cov.:

AF XY:

0.0163

AC XY:

1214

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00385

Gnomad4 AMR

AF:

0.0263

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.0153

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.00505

Hom.:

Bravo

AF:

0.0199

Asia WGS

AF:

0.140

AC:

485

AN:

3476

EpiCase

AF:

0.00115

EpiControl

AF:

0.000653

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 29, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Progressive familial intrahepatic cholestasis type 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

DANN

Benign

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over