rs12720464

Positions:

• chr7-87602537-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265724.8(ABCB1):​c.-330-1459G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 152,054 control chromosomes in the GnomAD database, including 211 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 0.017 (211 hom., cov: 32)
• Consequence: ABCB1 ENST00000265724.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCB1	NM_000927.5	c.-330-1459G>A		intron_variant			NP_000918.2
ABCB1	NM_001348944.2	c.-183-1459G>A		intron_variant			NP_001335873.1
ABCB1	NM_001348945.2	c.27+423G>A		intron_variant			NP_001335874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCB1	ENST00000265724.8	c.-330-1459G>A		intron_variant		1		ENSP00000265724	P1
ABCB1	ENST00000416177.1	c.-183-1459G>A		intron_variant		5		ENSP00000399419
ABCB1	ENST00000543898.5	c.-330-1459G>A		intron_variant		5		ENSP00000444095
ABCB1	ENST00000476862.1	n.316+423G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2585 AN: 151936 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.00608

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000912

Gnomad OTH AF: 0.0158

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

GnomAD4 genome AF: 0.0171 AC: 2594 AN: 152054 Hom.: 211 Cov.: 32 AF XY: 0.0184 AC XY: 1370 AN XY: 74336

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0340

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.00608

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.00603 Hom.: 46

Bravo AF: 0.0210

Asia WGS AF: 0.109 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.4
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12720464; hg19: chr7-87231853;