2-169013785-C-A

Position:

• chr2-169013785-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003742.4(ABCB11):​c.151-275G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,006 control chromosomes in the GnomAD database, including 2,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2850 hom., cov: 32)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0920

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-169013785-C-A is Benign according to our data. Variant chr2-169013785-C-A is described in ClinVar as [Benign]. Clinvar id is 1235141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB11	NM_003742.4	c.151-275G>T		intron_variant		ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1	c.151-275G>T		intron_variant			NM_003742.4	ENSP00000497931.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22772 AN: 151888 Hom.: 2831 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.0814

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.150 AC: 22834 AN: 152006 Hom.: 2850 Cov.: 32 AF XY: 0.150 AC XY: 11157 AN XY: 74306

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.0816

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.0569

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0682 Hom.: 1068

Bravo AF: 0.161

Asia WGS AF: 0.233 AC: 809 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs2241339; hg19: chr2-169870295;