Variant chr2-168973645-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003742.4(ABCB11):c.1434+70C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,556,316 control chromosomes in the GnomAD database, including 274,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25203 hom., cov: 31)

Exomes 𝑓: 0.59 ( 248905 hom. )

Consequence

ABCB11
NM_003742.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0960

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

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

BP6

Variant 2-168973645-G-A is Benign according to our data. Variant chr2-168973645-G-A is described in ClinVar as [Benign]. Clinvar id is 1184648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB11	NM_003742.4 linkuse as main transcript	c.1434+70C>T		intron_variant		ENST00000650372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB11	ENST00000650372.1 linkuse as main transcript	c.1434+70C>T		intron_variant			NM_003742.4	P1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86941

AN:

151612

Hom.:

25189

Cov.:

show subpopulations

Gnomad AFR

AF:

0.567

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.575

Gnomad EAS

AF:

0.750

Gnomad SAS

AF:

0.568

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.597

Gnomad OTH

AF:

0.580

GnomAD4 exome

AF:

0.593

AC:

833197

AN:

1404586

Hom.:

248905

AF XY:

0.592

AC XY:

412344

AN XY:

695948

show subpopulations

Gnomad4 AFR exome

AF:

0.578

Gnomad4 AMR exome

AF:

0.421

Gnomad4 ASJ exome

AF:

0.562

Gnomad4 EAS exome

AF:

0.752

Gnomad4 SAS exome

AF:

0.567

Gnomad4 FIN exome

AF:

0.511

Gnomad4 NFE exome

AF:

0.602

Gnomad4 OTH exome

AF:

0.589

GnomAD4 genome

AF:

0.573

AC:

86991

AN:

151730

Hom.:

25203

Cov.:

AF XY:

0.568

AC XY:

42068

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.567

Gnomad4 AMR

AF:

0.463

Gnomad4 ASJ

AF:

0.575

Gnomad4 EAS

AF:

0.749

Gnomad4 SAS

AF:

0.569

Gnomad4 FIN

AF:

0.513

Gnomad4 NFE

AF:

0.597

Gnomad4 OTH

AF:

0.583

Alfa

AF:

0.597

Hom.:

59174

Bravo

AF:

0.572

Asia WGS

AF:

0.670

AC:

2330

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Benign recurrent intrahepatic cholestasis type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Progressive familial intrahepatic cholestasis type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

DANN

Benign

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over