rs2685814

Variant names:

• chr2-168942109-T-C
• rs2685814
• NM_003742.4:c.2610+2496A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003742.4(ABCB11):​c.2610+2496A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 151,628 control chromosomes in the GnomAD database, including 20,041 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.50 (20041 hom., cov: 31)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.706
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.2610+2496A>G		intron_variant	Intron 21 of 27	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.2610+2496A>G		intron_variant	Intron 21 of 27		NM_003742.4	ENSP00000497931.1
ABCB11	ENST00000649448.1	c.927+2496A>G		intron_variant	Intron 7 of 14			ENSP00000497165.1
ABCB11	ENST00000439188.1	n.*1080+2496A>G		intron_variant	Intron 8 of 14	2		ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76457 AN: 151510 Hom.: 20044 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.504 AC: 76474 AN: 151628 Hom.: 20041 Cov.: 31 AF XY: 0.511 AC XY: 37879 AN XY: 74086

African (AFR) AF: 0.365 AC: 15107 AN: 41424

American (AMR) AF: 0.532 AC: 8062 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2157 AN: 3464

East Asian (EAS) AF: 0.631 AC: 3238 AN: 5132

South Asian (SAS) AF: 0.663 AC: 3192 AN: 4812

European-Finnish (FIN) AF: 0.571 AC: 6014 AN: 10532

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36765 AN: 67782

Other (OTH) AF: 0.516 AC: 1088 AN: 2108

Alfa AF: 0.543 Hom.: 12780

Bravo AF: 0.493

Asia WGS AF: 0.617 AC: 2128 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.0
DANN	Benign	0.88
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2685814; hg19: chr2-169798619;