rs1202175

Variant names:

• chr7-87579834-G-A
• rs1202175
• NM_001348946.2:c.286+5678C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-87579834-G-A
• chr7-87579834-G-C

Variant summary

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

The NM_001348945.2(ABCB1):​c.496+5678C>T 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 151,964 control chromosomes in the GnomAD database, including 37,731 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 (37731 hom., cov: 31)
• Consequence: ABCB1 NM_001348945.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348945.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.286+5678C>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.496+5678C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.286+5678C>T		intron	N/A	NP_000918.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.286+5678C>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.286+5678C>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000890305.1		c.286+5678C>T		intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106417 AN: 151844 Hom.: 37705 Cov.: 31

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.744

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: 106496 AN: 151964 Hom.: 37731 Cov.: 31 AF XY: 0.708 AC XY: 52571 AN XY: 74280

African (AFR) AF: 0.695 AC: 28786 AN: 41444

American (AMR) AF: 0.769 AC: 11745 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2311 AN: 3464

East Asian (EAS) AF: 0.982 AC: 5094 AN: 5188

South Asian (SAS) AF: 0.838 AC: 4033 AN: 4812

European-Finnish (FIN) AF: 0.698 AC: 7360 AN: 10546

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.662 AC: 44988 AN: 67930

Other (OTH) AF: 0.700 AC: 1474 AN: 2106

Alfa AF: 0.674 Hom.: 39820

Bravo AF: 0.706

Asia WGS AF: 0.880 AC: 3047 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.39
PhyloP100		0.34
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: rs1202175; hg19: chr7-87209150;