NM_001348946.2:c.287-3076G>A

Variant names:

• chr7-87573299-C-T
• rs10264990
• NM_001348946.2:c.287-3076G>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.287-3076G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,022 control chromosomes in the GnomAD database, including 38,581 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 0.71 (38581 hom., cov: 31)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• Publications: 15 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.856 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.287-3076G>A		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.497-3076G>A		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.287-3076G>A		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.287-3076G>A		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.287-3076G>A		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000890305.1		c.287-3076G>A		intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107714 AN: 151906 Hom.: 38555 Cov.: 31

Gnomad AFR AF: 0.785

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.709 AC: 107789 AN: 152022 Hom.: 38581 Cov.: 31 AF XY: 0.711 AC XY: 52858 AN XY: 74292

African (AFR) AF: 0.785 AC: 32557 AN: 41478

American (AMR) AF: 0.640 AC: 9781 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2178 AN: 3468

East Asian (EAS) AF: 0.877 AC: 4522 AN: 5156

South Asian (SAS) AF: 0.808 AC: 3897 AN: 4822

European-Finnish (FIN) AF: 0.713 AC: 7537 AN: 10572

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.664 AC: 45130 AN: 67928

Other (OTH) AF: 0.665 AC: 1404 AN: 2110

Alfa AF: 0.673 Hom.: 62069

Bravo AF: 0.708

Asia WGS AF: 0.823 AC: 2858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		-0.39
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: rs10264990; hg19: chr7-87202615;