rs1055302

Variant names:

• chr7-87503600-C-T
• rs1055302
• NM_001348946.2:c.*643G>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.*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
• Publications: 17 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.*643G>A		3_prime_UTR_variant	Exon 28 of 28	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.*643G>A		3_prime_UTR_variant	Exon 32 of 32		NP_001335874.1
ABCB1	NM_000927.5	c.*643G>A		3_prime_UTR_variant	Exon 29 of 29		NP_000918.2
ABCB1	NM_001348944.2	c.*643G>A		3_prime_UTR_variant	Exon 30 of 30		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.*643G>A		3_prime_UTR_variant	Exon 28 of 28	1	NM_001348946.2	ENSP00000478255.1

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.154 AC: 73 AN: 474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8

East Asian (EAS) AF: 0.207 AC: 12 AN: 58

South Asian (SAS) AF: 0.0769 AC: 12 AN: 156

European-Finnish (FIN) AF: 0.333 AC: 2 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.113 AC: 154 AN: 1360

Other (OTH) AF: 0.197 AC: 15 AN: 76

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

African (AFR) AF: 0.307 AC: 12731 AN: 41450

American (AMR) AF: 0.147 AC: 2247 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3472

East Asian (EAS) AF: 0.268 AC: 1382 AN: 5166

South Asian (SAS) AF: 0.146 AC: 703 AN: 4820

European-Finnish (FIN) AF: 0.141 AC: 1493 AN: 10556

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9088 AN: 67946

Other (OTH) AF: 0.184 AC: 389 AN: 2114

Alfa AF: 0.148 Hom.: 3057

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
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs1055302; hg19: chr7-87132916;