NM_001348946.2:c.2686-2598G>T

Variant names:

• chr7-87523474-C-A
• rs2141849
• NM_001348946.2:c.2686-2598G>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.2686-2598G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 151,854 control chromosomes in the GnomAD database, including 1,219 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 0.097 (1219 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.361 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.2686-2598G>T		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.2896-2598G>T		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.2686-2598G>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.2686-2598G>T		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.2686-2598G>T		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000488737.6	TSL:1	n.328-2598G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14697 AN: 151736 Hom.: 1212 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.0686

Gnomad FIN AF: 0.0640

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0909

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

GnomAD4 genome AF: 0.0969 AC: 14715 AN: 151854 Hom.: 1219 Cov.: 32 AF XY: 0.0995 AC XY: 7388 AN XY: 74238

African (AFR) AF: 0.174 AC: 7185 AN: 41396

American (AMR) AF: 0.102 AC: 1562 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 193 AN: 3464

East Asian (EAS) AF: 0.374 AC: 1921 AN: 5130

South Asian (SAS) AF: 0.0679 AC: 326 AN: 4804

European-Finnish (FIN) AF: 0.0640 AC: 676 AN: 10566

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0379 AC: 2574 AN: 67934

Other (OTH) AF: 0.0938 AC: 198 AN: 2112

Alfa AF: 0.0731 Hom.: 90

Bravo AF: 0.107

Asia WGS AF: 0.200 AC: 692 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.4
DANN	Benign	0.80
PhyloP100		0.68
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: rs2141849; hg19: chr7-87152790;