rs58898486

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000622132.5(ABCB1):​c.69-76C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00556 in 1,170,324 control chromosomes in the GnomAD database, including 36 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 0.0052 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0056 ( 31 hom. )

Consequence

ABCB1
ENST00000622132.5 intron

Scores

2

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: -0.654
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 -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BS2
High AC in GnomAd4 at 784 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCB1NM_001348946.2 linkuse as main transcriptc.69-76C>A intron_variant ENST00000622132.5 NP_001335875.1
ABCB1NM_000927.5 linkuse as main transcriptc.69-76C>A intron_variant NP_000918.2
ABCB1NM_001348944.2 linkuse as main transcriptc.69-76C>A intron_variant NP_001335873.1
ABCB1NM_001348945.2 linkuse as main transcriptc.279-76C>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.69-76C>A intron_variant 1 NM_001348946.2 ENSP00000478255 P1P08183-1
ABCB1ENST00000265724.8 linkuse as main transcriptc.69-76C>A intron_variant 1 ENSP00000265724 P1P08183-1
ABCB1ENST00000416177.1 linkuse as main transcriptc.69-76C>A intron_variant 5 ENSP00000399419
ABCB1ENST00000543898.5 linkuse as main transcriptc.69-76C>A intron_variant 5 ENSP00000444095 P08183-2

Frequencies

GnomAD3 genomes
AF:
0.00517
AC:
785
AN:
151858
Hom.:
5
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00106
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00387
Gnomad ASJ
AF:
0.00231
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00187
Gnomad FIN
AF:
0.0206
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00641
Gnomad OTH
AF:
0.00574
GnomAD4 exome
AF:
0.00562
AC:
5719
AN:
1018348
Hom.:
31
AF XY:
0.00545
AC XY:
2857
AN XY:
524326
show subpopulations
Gnomad4 AFR exome
AF:
0.000794
Gnomad4 AMR exome
AF:
0.00365
Gnomad4 ASJ exome
AF:
0.00178
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00201
Gnomad4 FIN exome
AF:
0.0174
Gnomad4 NFE exome
AF:
0.00589
Gnomad4 OTH exome
AF:
0.00554
GnomAD4 genome
AF:
0.00516
AC:
784
AN:
151976
Hom.:
5
Cov.:
32
AF XY:
0.00574
AC XY:
426
AN XY:
74278
show subpopulations
Gnomad4 AFR
AF:
0.00106
Gnomad4 AMR
AF:
0.00387
Gnomad4 ASJ
AF:
0.00231
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00187
Gnomad4 FIN
AF:
0.0206
Gnomad4 NFE
AF:
0.00639
Gnomad4 OTH
AF:
0.00568
Alfa
AF:
0.00545
Hom.:
1
Bravo
AF:
0.00429
Asia WGS
AF:
0.000581
AC:
2
AN:
3456

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
-0.88
CADD
Benign
0.17
DANN
Benign
0.48

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: rs58898486; hg19: chr7-87225206; API