chr7-87423890-G-A

Position:

• chr7-87423890-G-A

Variant summary

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

The NM_000443.4(ABCB4):​c.2211+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 1,613,788 control chromosomes in the GnomAD database, including 678,063 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64300 hom., cov: 31)
  • Exomes 𝑓: 0.92 (613763 hom.)
• Consequence: ABCB4 NM_000443.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.67

Genes affected

ABCB4 (HGNC:45): (ATP binding cassette subfamily B member 4) 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 as well as antigen presentation. This gene encodes a full transporter and member of the p-glycoprotein family of membrane proteins with phosphatidylcholine as its substrate. The function of this protein has not yet been determined; however, it may involve transport of phospholipids from liver hepatocytes into bile. Alternative splicing of this gene results in several products of undetermined function. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-87423890-G-A is Benign according to our data. Variant chr7-87423890-G-A is described in ClinVar as [Benign]. Clinvar id is 256161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-87423890-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB4	NM_000443.4	c.2211+16C>T		intron_variant		ENST00000649586.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB4	ENST00000649586.2	c.2211+16C>T		intron_variant			NM_000443.4	P1

Frequencies

GnomAD3 genomes AF: 0.918 AC: 139627 AN: 152096 Hom.: 64255 Cov.: 31

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.927

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.936

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.921

GnomAD3 exomes AF: 0.897 AC: 225437 AN: 251260 Hom.: 101616 AF XY: 0.898 AC XY: 121993 AN XY: 135790

Gnomad AFR exome AF: 0.936

Gnomad AMR exome AF: 0.878

Gnomad ASJ exome AF: 0.896

Gnomad EAS exome AF: 0.706

Gnomad SAS exome AF: 0.886

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.925

Gnomad OTH exome AF: 0.911

GnomAD4 exome AF: 0.915 AC: 1337974 AN: 1461574 Hom.: 613763 Cov.: 48 AF XY: 0.915 AC XY: 665006 AN XY: 727096

Gnomad4 AFR exome AF: 0.939

Gnomad4 AMR exome AF: 0.883

Gnomad4 ASJ exome AF: 0.896

Gnomad4 EAS exome AF: 0.705

Gnomad4 SAS exome AF: 0.889

Gnomad4 FIN exome AF: 0.928

Gnomad4 NFE exome AF: 0.926

Gnomad4 OTH exome AF: 0.906

GnomAD4 genome AF: 0.918 AC: 139728 AN: 152214 Hom.: 64300 Cov.: 31 AF XY: 0.919 AC XY: 68343 AN XY: 74406

Gnomad4 AFR AF: 0.933

Gnomad4 AMR AF: 0.926

Gnomad4 ASJ AF: 0.901

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.936

Gnomad4 NFE AF: 0.922

Gnomad4 OTH AF: 0.918

Alfa AF: 0.919 Hom.: 88644

Bravo AF: 0.915

Asia WGS AF: 0.820 AC: 2850 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 24, 2018	- -

Cholestasis, intrahepatic, of pregnancy, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Progressive familial intrahepatic cholestasis type 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.55
DANN	Benign	0.49

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: rs31668; hg19: chr7-87053206; COSMIC: COSV55935714; COSMIC: COSV55935714;