7-87584068-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348946.2(ABCB1):​c.286+1444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,086 control chromosomes in the GnomAD database, including 37,767 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.70 ( 37767 hom., cov: 32)

Consequence

ABCB1
NM_001348946.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.387

Publications

5 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCB1NM_001348946.2 linkc.286+1444G>A intron_variant Intron 4 of 27 ENST00000622132.5 NP_001335875.1
ABCB1NM_001348945.2 linkc.496+1444G>A intron_variant Intron 8 of 31 NP_001335874.1
ABCB1NM_000927.5 linkc.286+1444G>A intron_variant Intron 5 of 28 NP_000918.2 P08183-1A4D1D2
ABCB1NM_001348944.2 linkc.286+1444G>A intron_variant Intron 6 of 29 NP_001335873.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCB1ENST00000622132.5 linkc.286+1444G>A intron_variant Intron 4 of 27 1 NM_001348946.2 ENSP00000478255.1 P08183-1
ABCB1ENST00000265724.8 linkc.286+1444G>A intron_variant Intron 5 of 28 1 ENSP00000265724.3 P08183-1
ABCB1ENST00000543898.5 linkc.286+1444G>A intron_variant Intron 5 of 27 5 ENSP00000444095.1 P08183-2

Frequencies

GnomAD3 genomes
AF:
0.701
AC:
106504
AN:
151968
Hom.:
37741
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.695
Gnomad AMI
AF:
0.536
Gnomad AMR
AF:
0.769
Gnomad ASJ
AF:
0.667
Gnomad EAS
AF:
0.982
Gnomad SAS
AF:
0.839
Gnomad FIN
AF:
0.698
Gnomad MID
AF:
0.741
Gnomad NFE
AF:
0.662
Gnomad OTH
AF:
0.700
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.701
AC:
106583
AN:
152086
Hom.:
37767
Cov.:
32
AF XY:
0.708
AC XY:
52613
AN XY:
74348
show subpopulations
African (AFR)
AF:
0.695
AC:
28814
AN:
41478
American (AMR)
AF:
0.769
AC:
11758
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.667
AC:
2315
AN:
3470
East Asian (EAS)
AF:
0.982
AC:
5078
AN:
5172
South Asian (SAS)
AF:
0.839
AC:
4048
AN:
4826
European-Finnish (FIN)
AF:
0.698
AC:
7371
AN:
10566
Middle Eastern (MID)
AF:
0.748
AC:
220
AN:
294
European-Non Finnish (NFE)
AF:
0.662
AC:
45010
AN:
67966
Other (OTH)
AF:
0.700
AC:
1481
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1624
3248
4872
6496
8120
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
828
1656
2484
3312
4140
<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:
0.674
Hom.:
42922
Bravo
AF:
0.706
Asia WGS
AF:
0.881
AC:
3061
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.7
DANN
Benign
0.74
PhyloP100
-0.39
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1202185; hg19: chr7-87213384; API