2-168988099-C-A

Variant names:

• chr2-168988099-C-A
• rs6759156
• NM_003742.4:c.909-1815G>T

Variant summary

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

The ENST00000650372.1(ABCB11):​c.909-1815G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,012 control chromosomes in the GnomAD database, including 36,969 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 0.69 (36969 hom., cov: 32)
• Consequence: ABCB11 ENST00000650372.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000650372.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	NM_003742.4	MANE Select	c.909-1815G>T		intron	N/A	NP_003733.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	ENST00000650372.1	MANE Select	c.909-1815G>T		intron	N/A	ENSP00000497931.1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105259 AN: 151896 Hom.: 36935 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.691

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

GnomAD4 genome AF: 0.693 AC: 105354 AN: 152012 Hom.: 36969 Cov.: 32 AF XY: 0.693 AC XY: 51508 AN XY: 74276

African (AFR) AF: 0.772 AC: 32000 AN: 41466

American (AMR) AF: 0.542 AC: 8271 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2417 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4175 AN: 5154

South Asian (SAS) AF: 0.754 AC: 3638 AN: 4824

European-Finnish (FIN) AF: 0.703 AC: 7429 AN: 10564

Middle Eastern (MID) AF: 0.651 AC: 190 AN: 292

European-Non Finnish (NFE) AF: 0.665 AC: 45192 AN: 67978

Other (OTH) AF: 0.695 AC: 1463 AN: 2106

Alfa AF: 0.670 Hom.: 39282

Bravo AF: 0.684

Asia WGS AF: 0.813 AC: 2829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.6
DANN	Benign	0.58
PhyloP100		-0.68
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: rs6759156; hg19: chr2-169844609;