7-87583942-C-T

Variant names:

• chr7-87583942-C-T
• rs1202186
• NM_001348946.2:c.286+1570G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(ABCB1):​c.286+1570G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 151,988 control chromosomes in the GnomAD database, including 37,533 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 (37533 hom., cov: 31)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 9 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• 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
ABCB1	NM_001348946.2	c.286+1570G>A		intron_variant	Intron 4 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.496+1570G>A		intron_variant	Intron 8 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.286+1570G>A		intron_variant	Intron 5 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.286+1570G>A		intron_variant	Intron 6 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.286+1570G>A		intron_variant	Intron 4 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.286+1570G>A		intron_variant	Intron 5 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.286+1570G>A		intron_variant	Intron 5 of 27	5		ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106134 AN: 151870 Hom.: 37507 Cov.: 31

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.698

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.699 AC: 106211 AN: 151988 Hom.: 37533 Cov.: 31 AF XY: 0.706 AC XY: 52417 AN XY: 74264

African (AFR) AF: 0.688 AC: 28533 AN: 41484

American (AMR) AF: 0.769 AC: 11747 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2312 AN: 3464

East Asian (EAS) AF: 0.982 AC: 5070 AN: 5164

South Asian (SAS) AF: 0.838 AC: 4044 AN: 4824

European-Finnish (FIN) AF: 0.699 AC: 7346 AN: 10514

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 44975 AN: 67934

Other (OTH) AF: 0.698 AC: 1476 AN: 2114

Alfa AF: 0.676 Hom.: 58263

Bravo AF: 0.704

Asia WGS AF: 0.880 AC: 3059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.51
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

Other links and lift over

dbSNP: rs1202186; hg19: chr7-87213258;