rs31668

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.67

Variant links:

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]

ABCB4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
ABCB4	NM_000443.4 linkuse as main transcript	c.2211+16C>T		intron_variant		ENST00000649586.2	NP_000434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB4	ENST00000649586.2 linkuse as main transcript	c.2211+16C>T		intron_variant			NM_000443.4	ENSP00000496956	P1	P21439-2

Frequencies

GnomAD3 genomes

AF:

0.918

AC:

139627

AN:

152096

Hom.:

64255

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.915

AC XY:

665006

AN XY:

727096

show subpopulations

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.:

AF XY:

0.919

AC XY:

68343

AN XY:

74406

show subpopulations

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:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Cholestasis, intrahepatic, of pregnancy, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over