ENST00000265724.8:c.-330-1017T>C

Variant names:

• chr7-87602095-A-G
• rs28746504
• ENST00000265724.8:c.-330-1017T>C

Variant summary

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

The ENST00000265724.8(ABCB1):​c.-330-1017T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 151,796 control chromosomes in the GnomAD database, including 209 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 0.051 (209 hom., cov: 32)
• Consequence: ABCB1 ENST00000265724.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• Publications: 4 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0838 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	NM_001348945.2		c.27+865T>C		intron	N/A	NP_001335874.1
	ABCB1	NM_000927.5		c.-330-1017T>C		intron	N/A	NP_000918.2
	ABCB1	NM_001348944.2		c.-183-1017T>C		intron	N/A	NP_001335873.1	P08183-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCB1	ENST00000265724.8	TSL:1	c.-330-1017T>C		intron	N/A	ENSP00000265724.3	P08183-1
	ABCB1	ENST00000961093.1		c.-183-1017T>C		intron	N/A	ENSP00000631152.1
	ABCB1	ENST00000543898.5	TSL:5	c.-330-1017T>C		intron	N/A	ENSP00000444095.1	P08183-2

Frequencies

GnomAD3 genomes AF: 0.0512 AC: 7770 AN: 151678 Hom.: 204 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.0498

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0581

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

GnomAD4 genome AF: 0.0514 AC: 7801 AN: 151796 Hom.: 209 Cov.: 32 AF XY: 0.0502 AC XY: 3722 AN XY: 74204

African (AFR) AF: 0.0862 AC: 3570 AN: 41416

American (AMR) AF: 0.0336 AC: 512 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3466

East Asian (EAS) AF: 0.0499 AC: 256 AN: 5132

South Asian (SAS) AF: 0.0314 AC: 151 AN: 4814

European-Finnish (FIN) AF: 0.0343 AC: 360 AN: 10506

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.0402 AC: 2731 AN: 67894

Other (OTH) AF: 0.0585 AC: 123 AN: 2104

Alfa AF: 0.0453 Hom.: 29

Bravo AF: 0.0517

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.13
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs28746504;

hg19: chr7-87231411;