NM_001348946.2:c.1000-524T>A

Variant names:

• chr7-87551362-A-T
• rs4728702
• NM_001348946.2:c.1000-524T>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.1000-524T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,162 control chromosomes in the GnomAD database, including 30,342 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 0.62 (30342 hom., cov: 34)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 7 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 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.1000-524T>A		intron	N/A	NP_001335875.1
	ABCB1	NM_001348945.2		c.1210-524T>A		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.1000-524T>A		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.1000-524T>A		intron	N/A	ENSP00000478255.1
	ABCB1	ENST00000265724.8	TSL:1	c.1000-524T>A		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.808-524T>A		intron	N/A	ENSP00000444095.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 94008 AN: 152044 Hom.: 30285 Cov.: 34

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.619 AC: 94135 AN: 152162 Hom.: 30342 Cov.: 34 AF XY: 0.612 AC XY: 45489 AN XY: 74384

African (AFR) AF: 0.806 AC: 33471 AN: 41510

American (AMR) AF: 0.573 AC: 8766 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2196 AN: 3468

East Asian (EAS) AF: 0.365 AC: 1893 AN: 5180

South Asian (SAS) AF: 0.402 AC: 1937 AN: 4824

European-Finnish (FIN) AF: 0.514 AC: 5436 AN: 10584

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38358 AN: 67984

Other (OTH) AF: 0.619 AC: 1308 AN: 2114

Alfa AF: 0.599 Hom.: 3468

Bravo AF: 0.632

Asia WGS AF: 0.429 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.70
PhyloP100		-0.40
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: rs4728702; hg19: chr7-87180678;