chr7-87522208-C-G

Variant names:

• chr7-87522208-C-G
• rs1882477
• NM_001348946.2:c.2686-1332G>C

Variant summary

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

The NM_001348946.2(ABCB1):​c.2686-1332G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,335,090 control chromosomes in the GnomAD database, including 36,034 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 0.29 (8838 hom., cov: 32)
  • Exomes 𝑓: 0.20 (27196 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773
• 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]

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2686-1332G>C		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.2686-1332G>C		intron_variant	Intron 21 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43537 AN: 151912 Hom.: 8805 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.197 AC: 233483 AN: 1183060 Hom.: 27196 Cov.: 18 AF XY: 0.195 AC XY: 117287 AN XY: 601554

African (AFR) AF: 0.599 AC: 17832 AN: 29790

American (AMR) AF: 0.255 AC: 11183 AN: 43788

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 5802 AN: 24502

East Asian (EAS) AF: 0.435 AC: 16769 AN: 38572

South Asian (SAS) AF: 0.219 AC: 17713 AN: 80828

European-Finnish (FIN) AF: 0.118 AC: 4516 AN: 38156

Middle Eastern (MID) AF: 0.194 AC: 715 AN: 3682

European-Non Finnish (NFE) AF: 0.169 AC: 147344 AN: 872284

Other (OTH) AF: 0.226 AC: 11609 AN: 51458

GnomAD4 genome AF: 0.287 AC: 43626 AN: 152030 Hom.: 8838 Cov.: 32 AF XY: 0.284 AC XY: 21089 AN XY: 74300

African (AFR) AF: 0.563 AC: 23355 AN: 41448

American (AMR) AF: 0.229 AC: 3502 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 796 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2248 AN: 5160

South Asian (SAS) AF: 0.225 AC: 1078 AN: 4792

European-Finnish (FIN) AF: 0.108 AC: 1141 AN: 10588

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10618 AN: 67976

Other (OTH) AF: 0.268 AC: 567 AN: 2116

Alfa AF: 0.228 Hom.: 687

Bravo AF: 0.311

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.87
PhyloP100		-0.77
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: rs1882477; hg19: chr7-87151524; COSMIC: COSV55960840; COSMIC: COSV55960840;