rs2109505

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000443.4(ABCB4):c.711A>T(p.Ile237Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,670 control chromosomes in the GnomAD database, including 31,385 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4073 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27312 hom. )

Consequence

ABCB4
NM_000443.4 splice_region, synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.477

Publications

49 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 7-87450090-T-A is Benign according to our data. Variant chr7-87450090-T-A is described in ClinVar as Benign. ClinVar VariationId is 256166.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.477 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB4	NM_000443.4 link	c.711A>T	p.Ile237Ile	splice_region_variant, synonymous_variant	Exon 8 of 28	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.711A>T	p.Ile237Ile	splice_region_variant, synonymous_variant	Exon 8 of 28		NM_000443.4	ENSP00000496956.2		P21439-2

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33748

AN:

151932

Hom.:

4061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.267

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.191

GnomAD2 exomes

AF:

0.207

AC:

51926

AN:

250966

AF XY:

0.206

show subpopulations

Gnomad AFR exome

AF:

0.314

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.199

Gnomad EAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.190

AC:

278276

AN:

1461620

Hom.:

27312

Cov.:

AF XY:

0.191

AC XY:

139164

AN XY:

727140

show subpopulations

African (AFR)

AF:

0.320

AC:

10728

AN:

33476

American (AMR)

AF:

0.198

AC:

8846

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5198

AN:

26130

East Asian (EAS)

AF:

0.272

AC:

10788

AN:

39694

South Asian (SAS)

AF:

0.241

AC:

20827

AN:

86258

European-Finnish (FIN)

AF:

0.197

AC:

10526

AN:

53330

Middle Eastern (MID)

AF:

0.212

AC:

1222

AN:

5766

European-Non Finnish (NFE)

AF:

0.178

AC:

197853

AN:

1111872

Other (OTH)

AF:

0.204

AC:

12288

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

13155

26311

39466

52622

65777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7240

14480

21720

28960

36200

<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:

0.222

AC:

33800

AN:

152050

Hom.:

4073

Cov.:

AF XY:

0.222

AC XY:

16519

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.311

AC:

12886

AN:

41436

American (AMR)

AF:

0.175

AC:

2670

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.204

AC:

710

AN:

3472

East Asian (EAS)

AF:

0.266

AC:

1372

AN:

5162

South Asian (SAS)

AF:

0.238

AC:

1148

AN:

4818

European-Finnish (FIN)

AF:

0.196

AC:

2076

AN:

10574

Middle Eastern (MID)

AF:

0.164

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.181

AC:

12324

AN:

67988

Other (OTH)

AF:

0.196

AC:

414

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1303

2606

3910

5213

6516

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<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:

0.187

Hom.:

2067

Bravo

AF:

0.224

Asia WGS

AF:

0.261

AC:

908

AN:

3478

EpiCase

AF:

0.178

EpiControl

AF:

0.176

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

- -

Jan 13, 2016

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. -

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

- -

Jul 13, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Cholestasis, intrahepatic, of pregnancy, 3

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Progressive familial intrahepatic cholestasis type 3

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

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

-0.24

CADD

Benign

8.4

(source)

DANN

Benign

0.84

PhyloP100

-0.48

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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