2-168932796-T-C

Variant names:

• chr2-168932796-T-C
• rs494874
• NM_003742.4:c.3057-263A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003742.4(ABCB11):​c.3057-263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 152,078 control chromosomes in the GnomAD database, including 42,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (42464 hom., cov: 31)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.950
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• progressive familial intrahepatic cholestasis type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• benign recurrent intrahepatic cholestasis type 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-168932796-T-C is Benign according to our data. Variant chr2-168932796-T-C is described in ClinVar as [Benign]. Clinvar id is 1274842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.3057-263A>G		intron_variant	Intron 23 of 27	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.3057-263A>G		intron_variant	Intron 23 of 27		NM_003742.4	ENSP00000497931.1

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112459 AN: 151960 Hom.: 42416 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.737

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.740 AC: 112564 AN: 152078 Hom.: 42464 Cov.: 31 AF XY: 0.746 AC XY: 55435 AN XY: 74338

African (AFR) AF: 0.849 AC: 35202 AN: 41484

American (AMR) AF: 0.778 AC: 11892 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2643 AN: 3472

East Asian (EAS) AF: 0.983 AC: 5100 AN: 5186

South Asian (SAS) AF: 0.816 AC: 3930 AN: 4818

European-Finnish (FIN) AF: 0.669 AC: 7065 AN: 10556

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44256 AN: 67964

Other (OTH) AF: 0.735 AC: 1551 AN: 2110

Alfa AF: 0.690 Hom.: 38398

Bravo AF: 0.755

Asia WGS AF: 0.870 AC: 3024 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs494874; hg19: chr2-169789306;