7-87540040-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001348946.2(ABCB1):​c.2320-695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 152,230 control chromosomes in the GnomAD database, including 782 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 0.088 ( 782 hom., cov: 32)

Consequence

ABCB1
NM_001348946.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.880
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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCB1NM_001348946.2 linkuse as main transcriptc.2320-695G>A intron_variant ENST00000622132.5 NP_001335875.1
ABCB1NM_000927.5 linkuse as main transcriptc.2320-695G>A intron_variant NP_000918.2
ABCB1NM_001348944.2 linkuse as main transcriptc.2320-695G>A intron_variant NP_001335873.1
ABCB1NM_001348945.2 linkuse as main transcriptc.2530-695G>A intron_variant NP_001335874.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCB1ENST00000622132.5 linkuse as main transcriptc.2320-695G>A intron_variant 1 NM_001348946.2 ENSP00000478255 P1P08183-1
ABCB1ENST00000265724.8 linkuse as main transcriptc.2320-695G>A intron_variant 1 ENSP00000265724 P1P08183-1
ABCB1ENST00000543898.5 linkuse as main transcriptc.2128-695G>A intron_variant 5 ENSP00000444095 P08183-2

Frequencies

GnomAD3 genomes
AF:
0.0884
AC:
13440
AN:
152112
Hom.:
782
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0250
Gnomad AMI
AF:
0.219
Gnomad AMR
AF:
0.0958
Gnomad ASJ
AF:
0.148
Gnomad EAS
AF:
0.0596
Gnomad SAS
AF:
0.146
Gnomad FIN
AF:
0.0477
Gnomad MID
AF:
0.130
Gnomad NFE
AF:
0.125
Gnomad OTH
AF:
0.0939
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0884
AC:
13451
AN:
152230
Hom.:
782
Cov.:
32
AF XY:
0.0874
AC XY:
6504
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0250
Gnomad4 AMR
AF:
0.0959
Gnomad4 ASJ
AF:
0.148
Gnomad4 EAS
AF:
0.0594
Gnomad4 SAS
AF:
0.147
Gnomad4 FIN
AF:
0.0477
Gnomad4 NFE
AF:
0.125
Gnomad4 OTH
AF:
0.0953
Alfa
AF:
0.120
Hom.:
572
Bravo
AF:
0.0886
Asia WGS
AF:
0.112
AC:
388
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.77
DANN
Benign
0.49

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.

Other links and lift over

dbSNP: rs12720067; hg19: chr7-87169356; API