rs1055302

Positions:

• chr7-87503600-C-T

Variant summary

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

The NM_001348946.2(ABCB1):​c.*643G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 154,150 control chromosomes in the GnomAD database, including 3,255 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 0.19 (3226 hom., cov: 32)
  • Exomes 𝑓: 0.13 (29 hom.)
• Consequence: ABCB1 NM_001348946.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.*643G>A		3_prime_UTR_variant	28/28	ENST00000622132.5
ABCB1	NM_000927.5	c.*643G>A		3_prime_UTR_variant	29/29
ABCB1	NM_001348944.2	c.*643G>A		3_prime_UTR_variant	30/30
ABCB1	NM_001348945.2	c.*643G>A		3_prime_UTR_variant	32/32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.*643G>A		3_prime_UTR_variant	28/28	1	NM_001348946.2	P1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28892 AN: 151890 Hom.: 3210 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.126 AC: 269 AN: 2142 Hom.: 29 Cov.: 0 AF XY: 0.121 AC XY: 137 AN XY: 1136

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.190 AC: 28943 AN: 152008 Hom.: 3226 Cov.: 32 AF XY: 0.190 AC XY: 14085 AN XY: 74310

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.184

Alfa AF: 0.143 Hom.: 2196

Bravo AF: 0.198

Asia WGS AF: 0.210 AC: 728 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1055302; hg19: chr7-87132916;