chr2-168945742-G-T

Variant names:

• chr2-168945742-G-T
• rs853787
• NM_003742.4:c.2344-781C>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.2344-781C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 151,738 control chromosomes in the GnomAD database, including 41,915 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 0.74 (41915 hom., cov: 31)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 9 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003742.4. 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.2344-781C>A		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.2344-781C>A		intron	N/A	ENSP00000497931.1
	ABCB11	ENST00000649448.1		c.661-781C>A		intron	N/A	ENSP00000497165.1
	ABCB11	ENST00000439188.1	TSL:2	n.*814-781C>A		intron	N/A	ENSP00000416058.1

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111727 AN: 151620 Hom.: 41871 Cov.: 31

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.960

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.737 AC: 111832 AN: 151738 Hom.: 41915 Cov.: 31 AF XY: 0.742 AC XY: 54998 AN XY: 74134

African (AFR) AF: 0.837 AC: 34680 AN: 41448

American (AMR) AF: 0.769 AC: 11703 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2578 AN: 3464

East Asian (EAS) AF: 0.960 AC: 4925 AN: 5130

South Asian (SAS) AF: 0.841 AC: 4048 AN: 4816

European-Finnish (FIN) AF: 0.674 AC: 7109 AN: 10552

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44338 AN: 67798

Other (OTH) AF: 0.733 AC: 1543 AN: 2104

Alfa AF: 0.681 Hom.: 81396

Bravo AF: 0.750

Asia WGS AF: 0.883 AC: 3070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.46
PhyloP100		-0.14
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: rs853787; hg19: chr2-169802252;