7-87509329-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001348946.2(ABCB1):c.3435T>C(p.Ile1145Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,756 control chromosomes in the GnomAD database, including 196,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 26668 hom., cov: 31)

Exomes 𝑓: 0.48 ( 169342 hom. )

Consequence

ABCB1
NM_001348946.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -2.52

Variant links:

Genes affected

ABCB1 (HGNC:40): (ATP binding cassette subfamily B member 1) 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 an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ABCB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-87509329-A-G is Benign according to our data. Variant chr7-87509329-A-G is described in ClinVar as [Benign]. Clinvar id is 225939.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-87509329-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2 link	c.3435T>C	p.Ile1145Ile	synonymous_variant	Exon 26 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 link	c.3645T>C	p.Ile1215Ile	synonymous_variant	Exon 30 of 32		NP_001335874.1
ABCB1	NM_000927.5 link	c.3435T>C	p.Ile1145Ile	synonymous_variant	Exon 27 of 29		NP_000918.2	P08183-1A4D1D2
ABCB1	NM_001348944.2 link	c.3435T>C	p.Ile1145Ile	synonymous_variant	Exon 28 of 30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5 link	c.3435T>C	p.Ile1145Ile	synonymous_variant	Exon 26 of 28	1	NM_001348946.2	ENSP00000478255.1		P08183-1

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86843

AN:

151852

Hom.:

26611

Cov.:

show subpopulations

Gnomad AFR

AF:

0.797

Gnomad AMI

AF:

0.575

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.379

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.469

Gnomad OTH

AF:

0.601

GnomAD3 exomes

AF:

0.504

AC:

126736

AN:

251312

Hom.:

33677

AF XY:

0.491

AC XY:

66644

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.802

Gnomad AMR exome

AF:

0.548

Gnomad ASJ exome

AF:

0.644

Gnomad EAS exome

AF:

0.632

Gnomad SAS exome

AF:

0.395

Gnomad FIN exome

AF:

0.387

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.475

AC:

694396

AN:

1461786

Hom.:

169342

Cov.:

AF XY:

0.472

AC XY:

342927

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.821

Gnomad4 AMR exome

AF:

0.547

Gnomad4 ASJ exome

AF:

0.648

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.396

Gnomad4 FIN exome

AF:

0.390

Gnomad4 NFE exome

AF:

0.461

Gnomad4 OTH exome

AF:

0.511

GnomAD4 genome

AF:

0.572

AC:

86962

AN:

151970

Hom.:

26668

Cov.:

AF XY:

0.569

AC XY:

42247

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.797

Gnomad4 AMR

AF:

0.569

Gnomad4 ASJ

AF:

0.653

Gnomad4 EAS

AF:

0.619

Gnomad4 SAS

AF:

0.413

Gnomad4 FIN

AF:

0.379

Gnomad4 NFE

AF:

0.469

Gnomad4 OTH

AF:

0.600

Alfa

AF:

0.497

Hom.:

44976

Bravo

AF:

0.599

Asia WGS

AF:

0.516

AC:

1794

AN:

3476

EpiCase

AF:

0.478

EpiControl

AF:

0.477

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 13, 2018

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. -

ABCB1-related disorder

Benign:1

Jul 21, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

MDR1 POLYMORPHISM

Benign:1

Jan 26, 2007

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Tramadol response

Other:1

Apr 28, 2018

Bruce Budowle Laboratory, University of North Texas Health Science Center

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- T:M1 = postmortem ratio or tramadol to O-desmethyltramadol; t-MP = model-based clustered metabolizer phenotype inferred from T:M1

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.022

DANN

Benign

0.56

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