NM_001348946.2:c.2481+1291C>T

Variant names:

• chr7-87535167-G-A
• rs10274587
• NM_001348946.2:c.2481+1291C>T

Variant summary

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

The NM_001348946.2(ABCB1):​c.2481+1291C>T 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 151,722 control chromosomes in the GnomAD database, including 1,270 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 (1270 hom., cov: 30)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.757
• Publications: 10 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348946.2	MANE Select	c.2481+1291C>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.2691+1291C>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2481+1291C>T		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.2481+1291C>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.2481+1291C>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.2289+1291C>T		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19091 AN: 151604 Hom.: 1264 Cov.: 30

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0602

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.126 AC: 19128 AN: 151722 Hom.: 1270 Cov.: 30 AF XY: 0.124 AC XY: 9168 AN XY: 74144

African (AFR) AF: 0.154 AC: 6345 AN: 41308

American (AMR) AF: 0.109 AC: 1668 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3466

East Asian (EAS) AF: 0.0600 AC: 309 AN: 5154

South Asian (SAS) AF: 0.151 AC: 724 AN: 4798

European-Finnish (FIN) AF: 0.0480 AC: 505 AN: 10512

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

European-Non Finnish (NFE) AF: 0.126 AC: 8546 AN: 67932

Other (OTH) AF: 0.125 AC: 263 AN: 2106

Alfa AF: 0.130 Hom.: 1665

Bravo AF: 0.130

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.39
PhyloP100		0.76
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: rs10274587; hg19: chr7-87164483;