NM_003742.4:c.909-17G>A

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.909-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,606,816 control chromosomes in the GnomAD database, including 4,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 2247 hom., cov: 32)

Exomes 𝑓: 0.027 ( 2157 hom. )

Consequence

ABCB11
NM_003742.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.635

Publications

1 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=-0.91).

BP6

Variant 2-168986301-C-T is Benign according to our data. Variant chr2-168986301-C-T is described in ClinVar as Benign. ClinVar VariationId is 259159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB11	NM_003742.4 link	c.909-17G>A		intron_variant	Intron 9 of 27	ENST00000650372.1	NP_003733.2	O95342

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB11	ENST00000650372.1 link	c.909-17G>A		intron_variant	Intron 9 of 27		NM_003742.4	ENSP00000497931.1		O95342

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15976

AN:

151964

Hom.:

2236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0515

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0315

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0852

GnomAD2 exomes

AF:

0.0391

AC:

9662

AN:

247360

AF XY:

0.0346

show subpopulations

Gnomad AFR exome

AF:

0.327

Gnomad AMR exome

AF:

0.0269

Gnomad ASJ exome

AF:

0.0257

Gnomad EAS exome

AF:

0.000613

Gnomad FIN exome

AF:

0.00343

Gnomad NFE exome

AF:

0.0203

Gnomad OTH exome

AF:

0.0297

GnomAD4 exome

AF:

0.0271

AC:

39372

AN:

1454734

Hom.:

2157

Cov.:

AF XY:

0.0262

AC XY:

18963

AN XY:

723928

show subpopulations

African (AFR)

AF:

0.325

AC:

10717

AN:

33026

American (AMR)

AF:

0.0301

AC:

1339

AN:

44540

Ashkenazi Jewish (ASJ)

AF:

0.0267

AC:

695

AN:

26028

East Asian (EAS)

AF:

0.000328

AC:

AN:

39652

South Asian (SAS)

AF:

0.0299

AC:

2568

AN:

85896

European-Finnish (FIN)

AF:

0.00393

AC:

209

AN:

53200

Middle Eastern (MID)

AF:

0.0519

AC:

232

AN:

4474

European-Non Finnish (NFE)

AF:

0.0192

AC:

21266

AN:

1107904

Other (OTH)

AF:

0.0389

AC:

2333

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

1546

3093

4639

6186

7732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

966

1932

2898

3864

4830

<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:

0.105

AC:

16024

AN:

152082

Hom.:

2247

Cov.:

AF XY:

0.101

AC XY:

7539

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.321

AC:

13301

AN:

41444

American (AMR)

AF:

0.0514

AC:

785

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0262

AC:

AN:

3470

East Asian (EAS)

AF:

0.000581

AC:

AN:

5162

South Asian (SAS)

AF:

0.0309

AC:

149

AN:

4822

European-Finnish (FIN)

AF:

0.00358

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0215

AC:

1465

AN:

67990

Other (OTH)

AF:

0.0848

AC:

179

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

595

1190

1785

2380

2975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

288

432

576

720

<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:

0.0631

Hom.:

196

Bravo

AF:

0.118

Asia WGS

AF:

0.0390

AC:

135

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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

- -

Jan 27, 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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.91

CADD

Benign

2.2

(source)

DANN

Benign

0.49

PhyloP100

0.64

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

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