NM_001348946.2:c.1000-1021G>A

Variant names:

• chr7-87551859-C-T
• rs12704364
• NM_001348946.2:c.1000-1021G>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.1000-1021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,400 control chromosomes in the GnomAD database, including 17,407 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 0.48 (17407 hom., cov: 31)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.768
• Publications: 11 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.497 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.1000-1021G>A		intron	N/A	NP_001335875.1	P08183-1
	ABCB1	NM_001348945.2		c.1210-1021G>A		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.1000-1021G>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.1000-1021G>A		intron	N/A	ENSP00000478255.1	P08183-1
	ABCB1	ENST00000265724.8	TSL:1	c.1000-1021G>A		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000890305.1		c.1000-1021G>A		intron	N/A	ENSP00000560364.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72467 AN: 151282 Hom.: 17387 Cov.: 31

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.479 AC: 72531 AN: 151400 Hom.: 17407 Cov.: 31 AF XY: 0.475 AC XY: 35084 AN XY: 73896

African (AFR) AF: 0.486 AC: 20035 AN: 41258

American (AMR) AF: 0.507 AC: 7722 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1914 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1885 AN: 5146

South Asian (SAS) AF: 0.387 AC: 1859 AN: 4806

European-Finnish (FIN) AF: 0.385 AC: 3980 AN: 10338

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.492 AC: 33357 AN: 67838

Other (OTH) AF: 0.506 AC: 1067 AN: 2108

Alfa AF: 0.487 Hom.: 13526

Bravo AF: 0.487

Asia WGS AF: 0.390 AC: 1355 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.57
PhyloP100		0.77
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: rs12704364; hg19: chr7-87181175;