rs2373587

Positions:

• chr7-87528150-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001348946.2(ABCB1):​c.2685+3144G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 152,136 control chromosomes in the GnomAD database, including 1,230 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 0.097 (1230 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.662

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2685+3144G>C		intron_variant		ENST00000622132.5	NP_001335875.1
ABCB1	NM_000927.5	c.2685+3144G>C		intron_variant			NP_000918.2
ABCB1	NM_001348944.2	c.2685+3144G>C		intron_variant			NP_001335873.1
ABCB1	NM_001348945.2	c.2895+3144G>C		intron_variant			NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2685+3144G>C		intron_variant		1	NM_001348946.2	ENSP00000478255	P1

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14728 AN: 152018 Hom.: 1223 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.0670

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0915

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

GnomAD4 genome AF: 0.0969 AC: 14746 AN: 152136 Hom.: 1230 Cov.: 32 AF XY: 0.0996 AC XY: 7406 AN XY: 74384

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0557

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.0682

Gnomad4 FIN AF: 0.0639

Gnomad4 NFE AF: 0.0379

Gnomad4 OTH AF: 0.0943

Alfa AF: 0.0733 Hom.: 91

Bravo AF: 0.107

Asia WGS AF: 0.200 AC: 693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.50
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs2373587; hg19: chr7-87157466; COSMIC: COSV55946616;