rs2373589

Variant names:

• chr7-87522342-C-T
• rs2373589
• NM_001348946.2:c.2686-1466G>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.2686-1466G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 735,994 control chromosomes in the GnomAD database, including 17,860 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 0.23 (4541 hom., cov: 32)
  • Exomes 𝑓: 0.20 (13319 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 7 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]

HNRNPA1P9 (HGNC:39127): (heterogeneous nuclear ribonucleoprotein A1 pseudogene 9)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2686-1466G>A		intron_variant	Intron 21 of 27	ENST00000622132.5	NP_001335875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2686-1466G>A		intron_variant	Intron 21 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34315 AN: 151964 Hom.: 4524 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.198 AC: 115505 AN: 583912 Hom.: 13319 Cov.: 4 AF XY: 0.195 AC XY: 62609 AN XY: 320584

African (AFR) AF: 0.346 AC: 5871 AN: 16976

American (AMR) AF: 0.251 AC: 10673 AN: 42572

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 4183 AN: 19928

East Asian (EAS) AF: 0.453 AC: 15407 AN: 33988

South Asian (SAS) AF: 0.201 AC: 13926 AN: 69452

European-Finnish (FIN) AF: 0.125 AC: 4390 AN: 35062

Middle Eastern (MID) AF: 0.172 AC: 401 AN: 2328

European-Non Finnish (NFE) AF: 0.163 AC: 54300 AN: 332756

Other (OTH) AF: 0.206 AC: 6354 AN: 30850

GnomAD4 genome AF: 0.226 AC: 34371 AN: 152082 Hom.: 4541 Cov.: 32 AF XY: 0.225 AC XY: 16737 AN XY: 74330

African (AFR) AF: 0.340 AC: 14103 AN: 41458

American (AMR) AF: 0.209 AC: 3188 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3468

East Asian (EAS) AF: 0.454 AC: 2344 AN: 5158

South Asian (SAS) AF: 0.207 AC: 999 AN: 4824

European-Finnish (FIN) AF: 0.111 AC: 1180 AN: 10596

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11053 AN: 67984

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.206 Hom.: 548

Bravo AF: 0.242

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		1.5
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: rs2373589; hg19: chr7-87151658;