rs11568357

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003742.4(ABCB11):c.616A>G(p.Ile206Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000483 in 1,605,438 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I206I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

ABCB11
NM_003742.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.78

Publications

5 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 (MetaRNN=0.009624034).

BP6

Variant 2-168993878-T-C is Benign according to our data. Variant chr2-168993878-T-C is described in ClinVar as Benign. ClinVar VariationId is 287035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00274 (417/152236) while in subpopulation AFR AF = 0.00946 (393/41560). AF 95% confidence interval is 0.00869. There are 0 homozygotes in GnomAd4. There are 187 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003742.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB11	NM_003742.4	MANE Select	c.616A>G	p.Ile206Val	missense	Exon 8 of 28	NP_003733.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCB11	ENST00000650372.1	MANE Select	c.616A>G	p.Ile206Val	missense	Exon 8 of 28	ENSP00000497931.1	O95342
ABCB11	ENST00000858973.1		c.658A>G	p.Ile220Val	missense	Exon 8 of 28	ENSP00000529032.1
ABCB11	ENST00000858972.1		c.616A>G	p.Ile206Val	missense	Exon 8 of 27	ENSP00000529031.1

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00948

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000617

AC:

147

AN:

238334

AF XY:

0.000488

show subpopulations

Gnomad AFR exome

AF:

0.00887

Gnomad AMR exome

AF:

0.000276

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000277

Gnomad OTH exome

AF:

0.000516

GnomAD4 exome

AF:

0.000247

AC:

359

AN:

1453202

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

145

AN XY:

722586

show subpopulations

African (AFR)

AF:

0.00929

AC:

307

AN:

33038

American (AMR)

AF:

0.000348

AC:

AN:

43116

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25878

East Asian (EAS)

AF:

0.00

AC:

AN:

39440

South Asian (SAS)

AF:

0.00

AC:

AN:

84542

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53198

Middle Eastern (MID)

AF:

0.000872

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1108270

Other (OTH)

AF:

0.000450

AC:

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00274

AC:

417

AN:

152236

Hom.:

Cov.:

AF XY:

0.00251

AC XY:

187

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00946

AC:

393

AN:

41560

American (AMR)

AF:

0.00137

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000843

Hom.:

Bravo

AF:

0.00281

ESP6500AA

AF:

0.00865

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000829

AC:

100

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.22

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.65

PhyloP100

2.8

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.23

REVEL

Benign

0.18

Sift

Benign

0.63

Sift4G

Benign

0.65

Polyphen

0.0010

Vest4

0.075

MVP

0.75

MPC

0.13

ClinPred

0.0081

GERP RS

4.5

Varity_R

0.068

gMVP

0.53

Mutation Taster

=70/30

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over