7-87549310-C-T

Variant summary

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

The NM_001348946.2(ABCB1):​c.1725+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,612,476 control chromosomes in the GnomAD database, including 185,124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.48 ( 17440 hom., cov: 32)
Exomes 𝑓: 0.48 ( 167684 hom. )

Consequence

ABCB1
NM_001348946.2 intron

Scores

2

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.179
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=-0.81).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCB1NM_001348946.2 linkuse as main transcriptc.1725+38G>A intron_variant ENST00000622132.5 NP_001335875.1
ABCB1NM_000927.5 linkuse as main transcriptc.1725+38G>A intron_variant NP_000918.2
ABCB1NM_001348944.2 linkuse as main transcriptc.1725+38G>A intron_variant NP_001335873.1
ABCB1NM_001348945.2 linkuse as main transcriptc.1935+38G>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.1725+38G>A intron_variant 1 NM_001348946.2 ENSP00000478255 P1P08183-1
ABCB1ENST00000265724.8 linkuse as main transcriptc.1725+38G>A intron_variant 1 ENSP00000265724 P1P08183-1
ABCB1ENST00000543898.5 linkuse as main transcriptc.1533+38G>A intron_variant 5 ENSP00000444095 P08183-2
ABCB1ENST00000482527.1 linkuse as main transcriptn.479+38G>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.478
AC:
72594
AN:
151922
Hom.:
17420
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.484
Gnomad AMI
AF:
0.626
Gnomad AMR
AF:
0.506
Gnomad ASJ
AF:
0.552
Gnomad EAS
AF:
0.366
Gnomad SAS
AF:
0.384
Gnomad FIN
AF:
0.381
Gnomad MID
AF:
0.494
Gnomad NFE
AF:
0.491
Gnomad OTH
AF:
0.508
GnomAD3 exomes
AF:
0.459
AC:
114654
AN:
249540
Hom.:
26802
AF XY:
0.456
AC XY:
61429
AN XY:
134852
show subpopulations
Gnomad AFR exome
AF:
0.481
Gnomad AMR exome
AF:
0.471
Gnomad ASJ exome
AF:
0.557
Gnomad EAS exome
AF:
0.358
Gnomad SAS exome
AF:
0.378
Gnomad FIN exome
AF:
0.381
Gnomad NFE exome
AF:
0.497
Gnomad OTH exome
AF:
0.478
GnomAD4 exome
AF:
0.477
AC:
696533
AN:
1460434
Hom.:
167684
Cov.:
34
AF XY:
0.474
AC XY:
344613
AN XY:
726496
show subpopulations
Gnomad4 AFR exome
AF:
0.481
Gnomad4 AMR exome
AF:
0.472
Gnomad4 ASJ exome
AF:
0.566
Gnomad4 EAS exome
AF:
0.378
Gnomad4 SAS exome
AF:
0.379
Gnomad4 FIN exome
AF:
0.389
Gnomad4 NFE exome
AF:
0.491
Gnomad4 OTH exome
AF:
0.472
GnomAD4 genome
AF:
0.478
AC:
72659
AN:
152042
Hom.:
17440
Cov.:
32
AF XY:
0.473
AC XY:
35162
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.484
Gnomad4 AMR
AF:
0.506
Gnomad4 ASJ
AF:
0.552
Gnomad4 EAS
AF:
0.365
Gnomad4 SAS
AF:
0.385
Gnomad4 FIN
AF:
0.381
Gnomad4 NFE
AF:
0.491
Gnomad4 OTH
AF:
0.507
Alfa
AF:
0.496
Hom.:
29112
Bravo
AF:
0.487
Asia WGS
AF:
0.391
AC:
1362
AN:
3478

ClinVar

Significance: drug response
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Tramadol response Other:1
drug response, no assertion criteria providedresearchBruce Budowle Laboratory, University of North Texas Health Science CenterApr 28, 2018- 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
-0.81
CADD
Benign
5.1
DANN
Benign
0.55

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: rs2235013; hg19: chr7-87178626; COSMIC: COSV55951857; API