rs17149810

Variant names:

• chr7-87604673-C-T
• rs17149810
• ENST00000265724.8:c.-330-3595G>A

Variant summary

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

The NM_001348945.2(ABCB1):​c.-154-1533G>A 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 151,874 control chromosomes in the GnomAD database, including 3,261 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 (3261 hom., cov: 32)
• Consequence: ABCB1 NM_001348945.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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=-0.93).
• 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.-154-1533G>A		intron_variant	Intron 2 of 31		NP_001335874.1
ABCB1	NM_000927.5	c.-330-3595G>A		intron_variant	Intron 1 of 28		NP_000918.2
ABCB1	NM_001348944.2	c.-183-3595G>A		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.-330-3595G>A		intron_variant	Intron 1 of 28	1		ENSP00000265724.3
ABCB1	ENST00000543898.5	c.-330-3595G>A		intron_variant	Intron 1 of 27	5		ENSP00000444095.1
ABCB1	ENST00000416177.1	c.-183-3595G>A		intron_variant	Intron 1 of 5	5		ENSP00000399419.1
ABCB1	ENST00000476862.1	n.136-1533G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24069 AN: 151756 Hom.: 3236 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0606

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.159 AC: 24135 AN: 151874 Hom.: 3261 Cov.: 32 AF XY: 0.155 AC XY: 11540 AN XY: 74244

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0606

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.0638

Gnomad4 FIN AF: 0.0718

Gnomad4 NFE AF: 0.0673

Gnomad4 OTH AF: 0.149

Alfa AF: 0.0848 Hom.: 907

Bravo AF: 0.172

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.2
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17149810; hg19: chr7-87233989;