chr7-87522208-C-G

Position:

• chr7-87522208-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.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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.2686-1332G>C		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.2686-1332G>C		intron_variant
ABCB1	NM_001348944.2	c.2686-1332G>C		intron_variant
ABCB1	NM_001348945.2	c.2896-1332G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.2686-1332G>C		intron_variant		1	NM_001348946.2	P1
HNRNPA1P9	ENST00000450624.1	n.748C>G		non_coding_transcript_exon_variant	1/1

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

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.255

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.169

Gnomad4 OTH exome AF: 0.226

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

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.268

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

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: rs1882477; hg19: chr7-87151524; COSMIC: COSV55960840; COSMIC: COSV55960840;