ENST00000265724.8:c.-330-14566G>A

Variant names:

• chr7-87615644-C-T
• rs13233308
• ENST00000265724.8:c.-330-14566G>A

Variant summary

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

The ENST00000265724.8(ABCB1):​c.-330-14566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,066 control chromosomes in the GnomAD database, including 12,969 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 0.37 (12969 hom., cov: 32)
• Consequence: ABCB1 ENST00000265724.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.387
• Publications: 24 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 (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265724.8. 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_001348945.2		c.-154-12504G>A		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.-330-14566G>A		intron	N/A	NP_000918.2
	ABCB1	NM_001348944.2		c.-183-14566G>A		intron	N/A	NP_001335873.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000265724.8	TSL:1	c.-330-14566G>A		intron	N/A	ENSP00000265724.3
	ABCB1	ENST00000543898.5	TSL:5	c.-330-14566G>A		intron	N/A	ENSP00000444095.1
	ABCB1	ENST00000416177.1	TSL:5	c.-183-14566G>A		intron	N/A	ENSP00000399419.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56328 AN: 151948 Hom.: 12981 Cov.: 32

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.370 AC: 56303 AN: 152066 Hom.: 12969 Cov.: 32 AF XY: 0.375 AC XY: 27900 AN XY: 74312

African (AFR) AF: 0.0882 AC: 3662 AN: 41536

American (AMR) AF: 0.397 AC: 6069 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1477 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2436 AN: 5172

South Asian (SAS) AF: 0.648 AC: 3119 AN: 4816

European-Finnish (FIN) AF: 0.486 AC: 5120 AN: 10538

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33087 AN: 67948

Other (OTH) AF: 0.369 AC: 778 AN: 2110

Alfa AF: 0.455 Hom.: 32849

Bravo AF: 0.349

Asia WGS AF: 0.524 AC: 1817 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	3.5
DANN	Benign	0.58
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13233308; hg19: chr7-87244960;