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, 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	XM_017005165.2	c.3868-1879G>T		intron_variant	Intron 27 of 27		XP_016860654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000648875.1	c.226-1879G>T		intron_variant	Intron 2 of 2			ENSP00000497252.1

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 v4.3

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

Other links and lift over

dbSNP: rs563694; hg19: chr2-169774071;