Variant 7-87585559-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001348946.2(ABCB1):c.239C>A(p.Ala80Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

ABCB1
NM_001348946.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34465823).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2 linkuse as main transcript	c.239C>A	p.Ala80Glu	missense_variant	4/28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2 linkuse as main transcript	c.449C>A	p.Ala150Glu	missense_variant	8/32		NP_001335874.1
ABCB1	NM_000927.5 linkuse as main transcript	c.239C>A	p.Ala80Glu	missense_variant	5/29		NP_000918.2	P08183-1A4D1D2
ABCB1	NM_001348944.2 linkuse as main transcript	c.239C>A	p.Ala80Glu	missense_variant	6/30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ABCB1	ENST00000622132.5 linkuse as main transcript	c.239C>A	p.Ala80Glu	missense_variant	4/28	1	NM_001348946.2	ENSP00000478255.1	P08183-1
ABCB1	ENST00000265724.8 linkuse as main transcript	c.239C>A	p.Ala80Glu	missense_variant	5/29	1		ENSP00000265724.3	P08183-1
ABCB1	ENST00000543898.5 linkuse as main transcript	c.239C>A	p.Ala80Glu	missense_variant	5/28	5		ENSP00000444095.1	P08183-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251276

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461614

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000967

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Pathogenic

0.15

CADD

Benign

DANN

Benign

0.91

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.098

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.83

T;.;D

M_CAP

Benign

0.056

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Uncertain

2.5

M;M;M

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

.;N;N

REVEL

Uncertain

0.53

Sift

Uncertain

0.0060

.;D;D

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

0.69

P;P;.

Vest4

0.43

MutPred

0.46

Gain of disorder (P = 0.0989);Gain of disorder (P = 0.0989);Gain of disorder (P = 0.0989);

MVP

0.93

MPC

0.30

ClinPred

0.27

GERP RS

3.9

Varity_R

0.40

gMVP

0.72

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over