2-168958145-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003742.4(ABCB11):c.2179-17C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,605,162 control chromosomes in the GnomAD database, including 226,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17710 hom., cov: 31)

Exomes 𝑓: 0.53 ( 208838 hom. )

Consequence

ABCB11
NM_003742.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0820

Publications

21 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-168958145-G-T is Benign according to our data. Variant chr2-168958145-G-T is described in ClinVar as Benign. ClinVar VariationId is 259147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4 link	c.2179-17C>A		intron_variant	Intron 18 of 27	ENST00000650372.1	NP_003733.2	O95342

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCB11	ENST00000650372.1 link	c.2179-17C>A	intron_variant	Intron 18 of 27		NM_003742.4	ENSP00000497931.1	O95342
ABCB11	ENST00000649448.1 link	c.496-17C>A	intron_variant	Intron 4 of 14			ENSP00000497165.1	A0A3B3IS78
ABCB11	ENST00000439188.1 link	n.*649-17C>A	intron_variant	Intron 5 of 14	2		ENSP00000416058.1	H7C486

Frequencies

GnomAD3 genomes

AF:

0.466

AC:

70467

AN:

151290

Hom.:

17717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.272

Gnomad AMI

AF:

0.730

Gnomad AMR

AF:

0.517

Gnomad ASJ

AF:

0.592

Gnomad EAS

AF:

0.640

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.541

Gnomad NFE

AF:

0.524

Gnomad OTH

AF:

0.495

GnomAD2 exomes

AF:

0.547

AC:

133904

AN:

244912

AF XY:

0.553

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.597

Gnomad ASJ exome

AF:

0.605

Gnomad EAS exome

AF:

0.636

Gnomad FIN exome

AF:

0.527

Gnomad NFE exome

AF:

0.526

Gnomad OTH exome

AF:

0.535

GnomAD4 exome

AF:

0.532

AC:

774065

AN:

1453754

Hom.:

208838

Cov.:

AF XY:

0.537

AC XY:

388425

AN XY:

723142

show subpopulations

African (AFR)

AF:

0.264

AC:

8755

AN:

33220

American (AMR)

AF:

0.583

AC:

25969

AN:

44512

Ashkenazi Jewish (ASJ)

AF:

0.605

AC:

15678

AN:

25932

East Asian (EAS)

AF:

0.612

AC:

24210

AN:

39576

South Asian (SAS)

AF:

0.653

AC:

56085

AN:

85944

European-Finnish (FIN)

AF:

0.522

AC:

27480

AN:

52636

Middle Eastern (MID)

AF:

0.565

AC:

3145

AN:

5562

European-Non Finnish (NFE)

AF:

0.525

AC:

580707

AN:

1106370

Other (OTH)

AF:

0.534

AC:

32036

AN:

60002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16053

32106

48160

64213

80266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16734

33468

50202

66936

83670

<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:

0.465

AC:

70479

AN:

151408

Hom.:

17710

Cov.:

AF XY:

0.473

AC XY:

34984

AN XY:

73942

show subpopulations

African (AFR)

AF:

0.272

AC:

11252

AN:

41388

American (AMR)

AF:

0.518

AC:

7877

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.592

AC:

2045

AN:

3456

East Asian (EAS)

AF:

0.640

AC:

3257

AN:

5088

South Asian (SAS)

AF:

0.651

AC:

3136

AN:

4820

European-Finnish (FIN)

AF:

0.537

AC:

5659

AN:

10532

Middle Eastern (MID)

AF:

0.531

AC:

156

AN:

294

European-Non Finnish (NFE)

AF:

0.524

AC:

35408

AN:

67626

Other (OTH)

AF:

0.489

AC:

1026

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1807

3614

5422

7229

9036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

646

1292

1938

2584

3230

<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:

0.510

Hom.:

36046

Bravo

AF:

0.453

Asia WGS

AF:

0.605

AC:

2102

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

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

- -

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. -

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

- -

Progressive familial 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

-0.83

CADD

Benign

3.4

(source)

DANN

Benign

0.58

PhyloP100

0.082

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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