7-87513959-T-C

Variant names:

• chr7-87513959-T-C
• rs4148750
• NM_001348946.2:c.3282+1272A>G

Variant summary

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

The NM_001348946.2(ABCB1):​c.3282+1272A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,116 control chromosomes in the GnomAD database, including 4,046 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 0.17 (4046 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348946.2	c.3282+1272A>G		intron_variant	Intron 25 of 27	ENST00000622132.5	NP_001335875.1
ABCB1	NM_001348945.2	c.3492+1272A>G		intron_variant	Intron 29 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.3282+1272A>G		intron_variant	Intron 26 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.3282+1272A>G		intron_variant	Intron 27 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000622132.5	c.3282+1272A>G		intron_variant	Intron 25 of 27	1	NM_001348946.2	ENSP00000478255.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25380 AN: 151998 Hom.: 4030 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0639

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.167 AC: 25427 AN: 152116 Hom.: 4046 Cov.: 32 AF XY: 0.167 AC XY: 12435 AN XY: 74390

African (AFR) AF: 0.402 AC: 16638 AN: 41436

American (AMR) AF: 0.131 AC: 2002 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 353 AN: 3472

East Asian (EAS) AF: 0.376 AC: 1944 AN: 5164

South Asian (SAS) AF: 0.106 AC: 510 AN: 4818

European-Finnish (FIN) AF: 0.0639 AC: 677 AN: 10600

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0426 AC: 2897 AN: 68022

Other (OTH) AF: 0.150 AC: 316 AN: 2112

Alfa AF: 0.0805 Hom.: 660

Bravo AF: 0.186

Asia WGS AF: 0.226 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.9
DANN	Benign	0.57
PhyloP100		-0.64
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: rs4148750; hg19: chr7-87143275;