rs12720067

Positions:

• chr7-87540040-C-T

Variant summary

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

The NM_001348946.2(ABCB1):​c.2320-695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 152,230 control chromosomes in the GnomAD database, including 782 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 0.088 (782 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.2320-695G>A		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.2320-695G>A		intron_variant
ABCB1	NM_001348944.2	c.2320-695G>A		intron_variant
ABCB1	NM_001348945.2	c.2530-695G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.2320-695G>A		intron_variant		1	NM_001348946.2	P1
ABCB1	ENST00000265724.8	c.2320-695G>A		intron_variant		1		P1
ABCB1	ENST00000543898.5	c.2128-695G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13440 AN: 152112 Hom.: 782 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0958

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0939

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

GnomAD4 genome AF: 0.0884 AC: 13451 AN: 152230 Hom.: 782 Cov.: 32 AF XY: 0.0874 AC XY: 6504 AN XY: 74450

Gnomad4 AFR AF: 0.0250

Gnomad4 AMR AF: 0.0959

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0594

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0953

Alfa AF: 0.120 Hom.: 572

Bravo AF: 0.0886

Asia WGS AF: 0.112 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12720067; hg19: chr7-87169356;