2-169014345-A-G

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.108T>C(p.Asp36Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,040 control chromosomes in the GnomAD database, including 2,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 245 hom., cov: 32)

Exomes 𝑓: 0.012 ( 1793 hom. )

Consequence

ABCB11
NM_003742.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.574

Publications

19 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=-0.52).

BP6

Variant 2-169014345-A-G is Benign according to our data. Variant chr2-169014345-A-G is described in ClinVar as Benign. ClinVar VariationId is 259143.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.574 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4 link	c.108T>C	p.Asp36Asp	synonymous_variant	Exon 4 of 28	ENST00000650372.1	NP_003733.2	O95342

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1 link	c.108T>C	p.Asp36Asp	synonymous_variant	Exon 4 of 28		NM_003742.4	ENSP00000497931.1		O95342

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2263

AN:

152140

Hom.:

246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0263

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.0322

AC:

8013

AN:

248860

AF XY:

0.0277

show subpopulations

Gnomad AFR exome

AF:

0.00310

Gnomad AMR exome

AF:

0.0593

Gnomad ASJ exome

AF:

0.00965

Gnomad EAS exome

AF:

0.294

Gnomad FIN exome

AF:

0.000372

Gnomad NFE exome

AF:

0.000833

Gnomad OTH exome

AF:

0.0225

GnomAD4 exome

AF:

0.0115

AC:

16836

AN:

1460782

Hom.:

1793

Cov.:

AF XY:

0.0111

AC XY:

8042

AN XY:

726672

show subpopulations

African (AFR)

AF:

0.00182

AC:

AN:

33434

American (AMR)

AF:

0.0528

AC:

2361

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00942

AC:

246

AN:

26106

East Asian (EAS)

AF:

0.281

AC:

11156

AN:

39636

South Asian (SAS)

AF:

0.0105

AC:

906

AN:

86220

European-Finnish (FIN)

AF:

0.000394

AC:

AN:

53326

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000617

AC:

686

AN:

1111296

Other (OTH)

AF:

0.0230

AC:

1386

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

753

1507

2260

3014

3767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<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:

0.0148

AC:

2261

AN:

152258

Hom.:

245

Cov.:

AF XY:

0.0159

AC XY:

1183

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00363

AC:

151

AN:

41558

American (AMR)

AF:

0.0264

AC:

404

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0104

AC:

AN:

3472

East Asian (EAS)

AF:

0.292

AC:

1508

AN:

5168

South Asian (SAS)

AF:

0.0147

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000809

AC:

AN:

68012

Other (OTH)

AF:

0.0161

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

195

293

390

488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.00928

Hom.:

299

Bravo

AF:

0.0196

Asia WGS

AF:

0.134

AC:

465

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 29, 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. -

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

- -

Progressive familial intrahepatic cholestasis type 2

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.4

(source)

DANN

Benign

0.65

PhyloP100

0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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