2-168932506-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003742.4(ABCB11):c.3084A>G(p.Ala1028Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,612,724 control chromosomes in the GnomAD database, including 234,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A1028A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.47 ( 18356 hom., cov: 32)

Exomes 𝑓: 0.54 ( 216366 hom. )

Consequence

ABCB11
NM_003742.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -3.53

Publications

58 publications found

Variant links:

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]

ABCB11 Gene-Disease associations (from GenCC):

progressive familial intrahepatic cholestasis type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
benign recurrent intrahepatic cholestasis type 2
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ABCB11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-168932506-T-C is Benign according to our data. Variant chr2-168932506-T-C is described in ClinVar as Benign. ClinVar VariationId is 259152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4 link	c.3084A>G	p.Ala1028Ala	synonymous_variant	Exon 24 of 28	ENST00000650372.1	NP_003733.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1 link	c.3084A>G	p.Ala1028Ala	synonymous_variant	Exon 24 of 28		NM_003742.4	ENSP00000497931.1

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71727

AN:

151934

Hom.:

18361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.761

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.657

Gnomad FIN

AF:

0.559

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.498

GnomAD2 exomes

AF:

0.555

AC:

137322

AN:

247640

AF XY:

0.561

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.602

Gnomad ASJ exome

AF:

0.620

Gnomad EAS exome

AF:

0.619

Gnomad FIN exome

AF:

0.552

Gnomad NFE exome

AF:

0.536

Gnomad OTH exome

AF:

0.549

GnomAD4 exome

AF:

0.541

AC:

790142

AN:

1460672

Hom.:

216366

Cov.:

AF XY:

0.545

AC XY:

396148

AN XY:

726506

show subpopulations

African (AFR)

AF:

0.261

AC:

8742

AN:

33472

American (AMR)

AF:

0.588

AC:

26203

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

16266

AN:

26120

East Asian (EAS)

AF:

0.590

AC:

23424

AN:

39684

South Asian (SAS)

AF:

0.658

AC:

56646

AN:

86056

European-Finnish (FIN)

AF:

0.551

AC:

29397

AN:

53364

Middle Eastern (MID)

AF:

0.567

AC:

3272

AN:

5766

European-Non Finnish (NFE)

AF:

0.534

AC:

593441

AN:

1111290

Other (OTH)

AF:

0.543

AC:

32751

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

19208

38415

57623

76830

96038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16972

33944

50916

67888

84860

<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:

0.472

AC:

71733

AN:

152052

Hom.:

18356

Cov.:

AF XY:

0.480

AC XY:

35634

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.269

AC:

11134

AN:

41458

American (AMR)

AF:

0.512

AC:

7838

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.613

AC:

2127

AN:

3470

East Asian (EAS)

AF:

0.626

AC:

3227

AN:

5156

South Asian (SAS)

AF:

0.655

AC:

3153

AN:

4814

European-Finnish (FIN)

AF:

0.559

AC:

5904

AN:

10554

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.536

AC:

36458

AN:

67986

Other (OTH)

AF:

0.492

AC:

1039

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1836

3673

5509

7346

9182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

652

1304

1956

2608

3260

<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:

0.512

Hom.:

69025

Bravo

AF:

0.457

Asia WGS

AF:

0.603

AC:

2095

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

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 05, 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. -

Jul 13, 2016

Eurofins Ntd Llc (ga)

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive familial intrahepatic cholestasis type 2

Benign:3

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. -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Benign recurrent intrahepatic cholestasis type 2

Benign:1

Jul 10, 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

-0.87

CADD

Benign

0.041

(source)

DANN

Benign

0.41

PhyloP100

-3.5

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

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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