7-87511492-A-G

Variant names:

• chr7-87511492-A-G
• rs10808071
• NM_001348946.2:c.3283-2011T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000622132.5(ABCB1):​c.3283-2011T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,182 control chromosomes in the GnomAD database, including 3,075 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 0.20 (3075 hom., cov: 32)
• Consequence: ABCB1 ENST00000622132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.937
• Publications: 8 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000622132.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.3283-2011T>C		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.3493-2011T>C		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.3283-2011T>C		intron	N/A	NP_000918.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000622132.5	TSL:1 MANE Select	c.3283-2011T>C		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.3283-2011T>C		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000488737.6	TSL:1	n.925-2011T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29788 AN: 152064 Hom.: 3069 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0856

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29816 AN: 152182 Hom.: 3075 Cov.: 32 AF XY: 0.193 AC XY: 14378 AN XY: 74402

African (AFR) AF: 0.235 AC: 9776 AN: 41522

American (AMR) AF: 0.163 AC: 2488 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3472

East Asian (EAS) AF: 0.0852 AC: 442 AN: 5186

South Asian (SAS) AF: 0.165 AC: 795 AN: 4810

European-Finnish (FIN) AF: 0.150 AC: 1595 AN: 10598

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13252 AN: 68000

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.197 Hom.: 7661

Bravo AF: 0.200

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.94
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: rs10808071; hg19: chr7-87140808;