chr7-87533733-C-T

Variant names:

• chr7-87533733-C-T
• rs4148738
• NM_001348946.2:c.2482-2236G>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.2482-2236G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,930 control chromosomes in the GnomAD database, including 29,287 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 0.61 (29287 hom., cov: 31)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 81 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.2482-2236G>A		intron_variant	Intron 20 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.2692-2236G>A		intron_variant	Intron 24 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.2482-2236G>A		intron_variant	Intron 21 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.2482-2236G>A		intron_variant	Intron 22 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.2482-2236G>A		intron_variant	Intron 20 of 27	1	NM_001348946.2	ENSP00000478255.1
ABCB1	ENST00000265724.8	c.2482-2236G>A		intron_variant	Intron 21 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.2290-2236G>A		intron_variant	Intron 20 of 27	5		ENSP00000444095.1
ABCB1	ENST00000496821.5	n.110-2236G>A		intron_variant	Intron 2 of 6	5

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92820 AN: 151812 Hom.: 29236 Cov.: 31

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.612 AC: 92937 AN: 151930 Hom.: 29287 Cov.: 31 AF XY: 0.606 AC XY: 45020 AN XY: 74250

African (AFR) AF: 0.776 AC: 32150 AN: 41430

American (AMR) AF: 0.603 AC: 9197 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2161 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3102 AN: 5158

South Asian (SAS) AF: 0.405 AC: 1954 AN: 4822

European-Finnish (FIN) AF: 0.483 AC: 5100 AN: 10556

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37214 AN: 67934

Other (OTH) AF: 0.623 AC: 1314 AN: 2110

Alfa AF: 0.574 Hom.: 19650

Bravo AF: 0.630

Asia WGS AF: 0.522 AC: 1819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.24
PhyloP100		-1.1
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: rs4148738; hg19: chr7-87163049;