rs4728709

Variant names:

• chr7-87604286-G-A
• rs4728709
• ENST00000265724.8:c.-330-3208C>T

Variant summary

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

The ENST00000265724.8(ABCB1):​c.-330-3208C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,910 control chromosomes in the GnomAD database, including 3,253 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 0.16 (3253 hom., cov: 32)
• Consequence: ABCB1 ENST00000265724.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.83
• Publications: 41 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 (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCB1	NM_001348945.2	c.-154-1146C>T		intron_variant	Intron 2 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.-330-3208C>T		intron_variant	Intron 1 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.-183-3208C>T		intron_variant	Intron 1 of 29		NP_001335873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000265724.8	c.-330-3208C>T		intron_variant	Intron 1 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.-330-3208C>T		intron_variant	Intron 1 of 27	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.-183-3208C>T		intron_variant	Intron 1 of 5	5		ENSP00000399419.1
ABCB1	ENST00000476862.1	n.136-1146C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24054 AN: 151792 Hom.: 3228 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0603

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0676

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.149

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

GnomAD4 genome AF: 0.159 AC: 24121 AN: 151910 Hom.: 3253 Cov.: 32 AF XY: 0.155 AC XY: 11526 AN XY: 74226

African (AFR) AF: 0.373 AC: 15408 AN: 41356

American (AMR) AF: 0.114 AC: 1736 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0603 AC: 209 AN: 3464

East Asian (EAS) AF: 0.139 AC: 718 AN: 5158

South Asian (SAS) AF: 0.0674 AC: 324 AN: 4804

European-Finnish (FIN) AF: 0.0715 AC: 754 AN: 10550

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4574 AN: 67982

Other (OTH) AF: 0.149 AC: 313 AN: 2106

Alfa AF: 0.0967 Hom.: 2387

Bravo AF: 0.172

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.2
DANN	Benign	0.13
PhyloP100		1.8
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: rs4728709; hg19: chr7-87233602;