7-87550493-C-T

Position:

chr7-87550493-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001348946.2(ABCB1):c.1199G>A(p.Ser400Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,613,078 control chromosomes in the GnomAD database, including 1,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.026 ( 80 hom., cov: 33)

Exomes 𝑓: 0.033 ( 927 hom. )

Consequence

ABCB1
NM_001348946.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0700

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008169949).

BP6

Variant 7-87550493-C-T is Benign according to our data. Variant chr7-87550493-C-T is described in ClinVar as [Benign]. Clinvar id is 194008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-87550493-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0256 (3906/152282) while in subpopulation NFE AF= 0.0402 (2734/68006). AF 95% confidence interval is 0.0389. There are 80 homozygotes in gnomad4. There are 1815 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3906 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2 linkuse as main transcript	c.1199G>A	p.Ser400Asn	missense_variant	11/28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 linkuse as main transcript	c.1409G>A	p.Ser470Asn	missense_variant	15/32		NP_001335874.1
ABCB1	NM_000927.5 linkuse as main transcript	c.1199G>A	p.Ser400Asn	missense_variant	12/29		NP_000918.2	P08183-1A4D1D2
ABCB1	NM_001348944.2 linkuse as main transcript	c.1199G>A	p.Ser400Asn	missense_variant	13/30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.1199G>A	p.Ser400Asn	missense_variant	11/28	1	NM_001348946.2	ENSP00000478255.1	P08183-1
ABCB1	ENST00000265724.8 linkuse as main transcript	c.1199G>A	p.Ser400Asn	missense_variant	12/29	1		ENSP00000265724.3	P08183-1
ABCB1	ENST00000543898.5 linkuse as main transcript	c.1007G>A	p.Ser336Asn	missense_variant	11/28	5		ENSP00000444095.1	P08183-2

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3906

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00717

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0279

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.0151

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0402

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0274

AC:

6863

AN:

250840

Hom.:

116

AF XY:

0.0285

AC XY:

3870

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00597

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.0272

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0153

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.0432

Gnomad OTH exome

AF:

0.0240

GnomAD4 exome

AF:

0.0328

AC:

47905

AN:

1460796

Hom.:

927

Cov.:

AF XY:

0.0325

AC XY:

23654

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.00502

Gnomad4 AMR exome

AF:

0.0182

Gnomad4 ASJ exome

AF:

0.0271

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0147

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.0378

Gnomad4 OTH exome

AF:

0.0290

GnomAD4 genome

AF:

0.0256

AC:

3906

AN:

152282

Hom.:

Cov.:

AF XY:

0.0244

AC XY:

1815

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00715

Gnomad4 AMR

AF:

0.0279

Gnomad4 ASJ

AF:

0.0280

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0151

Gnomad4 NFE

AF:

0.0402

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0383

Hom.:

307

Bravo

AF:

0.0260

TwinsUK

AF:

0.0345

AC:

128

ALSPAC

AF:

0.0353

AC:

136

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.0385

AC:

331

ExAC

AF:

0.0290

AC:

3523

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.0477

EpiControl

AF:

0.0476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 22, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Oct 04, 2015	- -

ABCB1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 21, 2021

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.96

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.52

T;.;T

MetaRNN

Benign

0.0082

T;T;T

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.1

M;M;.

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.96

.;N;N

REVEL

Benign

0.26

Sift

Benign

0.36

.;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0040

B;B;.

Vest4

0.024

MPC

0.20

ClinPred

0.0092

GERP RS

3.0

Varity_R

0.15

gMVP

0.45

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