rs31668

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

progressive familial intrahepatic cholestasis type 3
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
gallbladder disease 1
Inheritance: SD, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
pancreatitis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ABCB4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 256161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
ABCB4	NM_000443.4 link	c.2211+16C>T		intron_variant	Intron 17 of 27	ENST00000649586.2	NP_000434.1	P21439-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB4	ENST00000649586.2 link	c.2211+16C>T		intron_variant	Intron 17 of 27		NM_000443.4	ENSP00000496956.2		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

GnomAD2 exomes

AF:

0.897

AC:

225437

AN:

251260

AF XY:

0.898

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 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

African (AFR)

AF:

0.939

AC:

31418

AN:

33468

American (AMR)

AF:

0.883

AC:

39498

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.896

AC:

23399

AN:

26126

East Asian (EAS)

AF:

0.705

AC:

27977

AN:

39688

South Asian (SAS)

AF:

0.889

AC:

76684

AN:

86256

European-Finnish (FIN)

AF:

0.928

AC:

49579

AN:

53410

Middle Eastern (MID)

AF:

0.921

AC:

5310

AN:

5764

European-Non Finnish (NFE)

AF:

0.926

AC:

1029432

AN:

1111760

Other (OTH)

AF:

0.906

AC:

54677

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

6112

12224

18336

24448

30560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21518

43036

64554

86072

107590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.918

AC:

139728

AN:

152214

Hom.:

64300

Cov.:

AF XY:

0.919

AC XY:

68343

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.933

AC:

38762

AN:

41546

American (AMR)

AF:

0.926

AC:

14160

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.901

AC:

3130

AN:

3472

East Asian (EAS)

AF:

0.709

AC:

3665

AN:

5168

South Asian (SAS)

AF:

0.888

AC:

4277

AN:

4814

European-Finnish (FIN)

AF:

0.936

AC:

9919

AN:

10596

Middle Eastern (MID)

AF:

0.939

AC:

276

AN:

294

European-Non Finnish (NFE)

AF:

0.922

AC:

62706

AN:

68014

Other (OTH)

AF:

0.918

AC:

1940

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

574

1148

1722

2296

2870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.920

Hom.:

111577

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

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jan 24, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cholestasis, intrahepatic, of pregnancy, 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive familial intrahepatic cholestasis type 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.55

(source)

DANN

Benign

0.49

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over