7-87531245-A-G

Variant names:

• chr7-87531245-A-G
• rs2032583
• NM_001348946.2:c.2685+49T>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.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
• Publications: 66 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001348946.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.2685+49T>C		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.2895+49T>C		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2685+49T>C		intron	N/A	NP_000918.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.2685+49T>C		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.2685+49T>C		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000488737.6	TSL:1	n.327+49T>C		intron	N/A

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

GnomAD2 exomes AF: 0.119 AC: 29480 AN: 247822 AF XY: 0.121

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 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

African (AFR) AF: 0.179 AC: 5437 AN: 30436

American (AMR) AF: 0.104 AC: 4630 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4052 AN: 25230

East Asian (EAS) AF: 0.0546 AC: 2124 AN: 38916

South Asian (SAS) AF: 0.151 AC: 12657 AN: 83576

European-Finnish (FIN) AF: 0.0527 AC: 2738 AN: 51910

Middle Eastern (MID) AF: 0.121 AC: 632 AN: 5226

European-Non Finnish (NFE) AF: 0.128 AC: 127526 AN: 999990

Other (OTH) AF: 0.129 AC: 7273 AN: 56192

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

African (AFR) AF: 0.171 AC: 7095 AN: 41540

American (AMR) AF: 0.111 AC: 1699 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3470

East Asian (EAS) AF: 0.0592 AC: 307 AN: 5186

South Asian (SAS) AF: 0.151 AC: 731 AN: 4830

European-Finnish (FIN) AF: 0.0474 AC: 504 AN: 10628

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.126 AC: 8545 AN: 67984

Other (OTH) AF: 0.128 AC: 270 AN: 2112

Alfa AF: 0.131 Hom.: 4566

Bravo AF: 0.136

Asia WGS AF: 0.124 AC: 432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.75
PhyloP100		0.28
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: rs2032583; hg19: chr7-87160561;