rs2032583

chr7-87531245-A-Gchr7-87531245-A-T

Variant summary

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

The NM_001348946.2(ABCB1):c.2685+49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,488,128 control chromosomes in the GnomAD database, including 12,483 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 0.13 (1388 hom., cov: 32)
  • Exomes 𝑓: 0.13 (11095 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.2685+49T>C		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.2685+49T>C		intron_variant
ABCB1	NM_001348944.2	c.2685+49T>C		intron_variant
ABCB1	NM_001348945.2	c.2895+49T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.2685+49T>C		intron_variant		1	NM_001348946.2	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19876 AN: 152126 Hom.: 1380 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.119 AC: 29480 AN: 247822 Hom.: 1965 AF XY: 0.121 AC XY: 16168 AN XY: 134118

Gnomad AFR exome AF: 0.175

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.0577

Gnomad SAS exome AF: 0.155

Gnomad FIN exome AF: 0.0500

Gnomad NFE exome AF: 0.125

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.125 AC: 167069 AN: 1335884 Hom.: 11095 Cov.: 20 AF XY: 0.126 AC XY: 84818 AN XY: 671948

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.0546

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.0527

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.131 AC: 19919 AN: 152244 Hom.: 1388 Cov.: 32 AF XY: 0.128 AC XY: 9520 AN XY: 74448

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0592

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.0474

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.128

Alfa AF: 0.133 Hom.: 2071

Bravo AF: 0.136

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.6
Dann	Benign	0.75

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: rs2032583; hg19: chr7-87160561;