2-168926529-G-T

Variant names:

• chr2-168926529-G-T
• rs579060
• NM_003742.4:c.3618+627C>A

Variant summary

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

The NM_003742.4(ABCB11):​c.3618+627C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,082 control chromosomes in the GnomAD database, including 41,623 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 0.73 (41623 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.3618+627C>A		intron_variant	Intron 26 of 27	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.3618+627C>A		intron_variant	Intron 26 of 27		NM_003742.4	ENSP00000497931.1
ABCB11	ENST00000649448.1	c.1995+627C>A		intron_variant	Intron 13 of 14			ENSP00000497165.1
ABCB11	ENST00000648875.1	c.78+627C>A		intron_variant	Intron 1 of 2			ENSP00000497252.1
ABCB11	ENST00000439188.1	n.*2016+627C>A		intron_variant	Intron 13 of 14	2		ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111390 AN: 151966 Hom.: 41583 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.733 AC: 111489 AN: 152082 Hom.: 41623 Cov.: 32 AF XY: 0.739 AC XY: 54951 AN XY: 74346

African (AFR) AF: 0.842 AC: 34950 AN: 41498

American (AMR) AF: 0.761 AC: 11623 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2627 AN: 3470

East Asian (EAS) AF: 0.969 AC: 5024 AN: 5184

South Asian (SAS) AF: 0.808 AC: 3894 AN: 4822

European-Finnish (FIN) AF: 0.667 AC: 7044 AN: 10558

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43872 AN: 67956

Other (OTH) AF: 0.727 AC: 1535 AN: 2112

Alfa AF: 0.679 Hom.: 76854

Bravo AF: 0.745

Asia WGS AF: 0.844 AC: 2934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.19
DANN	Benign	0.56
PhyloP100		-0.64
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: rs579060; hg19: chr2-169783039;