rs563694

Variant names:

• chr2-168917561-C-A
• rs563694
• ENST00000648875.1:c.226-1879G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-168917561-C-A
• chr2-168917561-C-G
• chr2-168917561-C-T

Variant summary

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

The ENST00000648875.1(ABCB11):​c.226-1879G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 152,158 control chromosomes in the GnomAD database, including 44,093 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 0.75 (44093 hom., cov: 32)
• Consequence: ABCB11 ENST00000648875.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 43 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, Labcorp Genetics (formerly Invitae), Orphanet
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000648875.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000648875.1		c.226-1879G>T		intron	N/A	ENSP00000497252.1	A0A3B3ISD4

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114489 AN: 152040 Hom.: 44034 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.962

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.753 AC: 114608 AN: 152158 Hom.: 44093 Cov.: 32 AF XY: 0.757 AC XY: 56343 AN XY: 74382

African (AFR) AF: 0.892 AC: 37043 AN: 41544

American (AMR) AF: 0.779 AC: 11906 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2595 AN: 3472

East Asian (EAS) AF: 0.961 AC: 4992 AN: 5192

South Asian (SAS) AF: 0.817 AC: 3934 AN: 4814

European-Finnish (FIN) AF: 0.670 AC: 7085 AN: 10578

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44549 AN: 67950

Other (OTH) AF: 0.746 AC: 1578 AN: 2116

Alfa AF: 0.693 Hom.: 102975

Bravo AF: 0.769

Asia WGS AF: 0.863 AC: 2998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.8
DANN	Benign	0.59
PhyloP100		0.065

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs563694;

hg19: chr2-169774071;