rs2287623

Positions:

• chr2-168973645-G-A
• chr2-168973645-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003742.4(ABCB11):​c.1434+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,556,316 control chromosomes in the GnomAD database, including 274,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25203 hom., cov: 31)
  • Exomes 𝑓: 0.59 (248905 hom.)
• Consequence: ABCB11 NM_003742.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0960

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-168973645-G-A is Benign according to our data. Variant chr2-168973645-G-A is described in ClinVar as [Benign]. Clinvar id is 1184648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB11	NM_003742.4	c.1434+70C>T		intron_variant		ENST00000650372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB11	ENST00000650372.1	c.1434+70C>T		intron_variant			NM_003742.4	P1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86941 AN: 151612 Hom.: 25189 Cov.: 31

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.568

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.593 AC: 833197 AN: 1404586 Hom.: 248905 AF XY: 0.592 AC XY: 412344 AN XY: 695948

Gnomad4 AFR exome AF: 0.578

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.567

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.602

Gnomad4 OTH exome AF: 0.589

GnomAD4 genome AF: 0.573 AC: 86991 AN: 151730 Hom.: 25203 Cov.: 31 AF XY: 0.568 AC XY: 42068 AN XY: 74120

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.575

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.583

Alfa AF: 0.597 Hom.: 59174

Bravo AF: 0.572

Asia WGS AF: 0.670 AC: 2330 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Benign recurrent intrahepatic cholestasis type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Progressive familial intrahepatic cholestasis type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.42

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: rs2287623; hg19: chr2-169830155; COSMIC: COSV55597948; COSMIC: COSV55597948;