rs1002204

chr7-87512181-A-Cchr7-87512181-A-Gchr7-87512181-A-T

Variant summary

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

The NM_001348946.2(ABCB1):c.3283-2700T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 150,446 control chromosomes in the GnomAD database, including 25,321 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 0.57 (25321 hom., cov: 29)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.3283-2700T>G		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.3283-2700T>G		intron_variant
ABCB1	NM_001348944.2	c.3283-2700T>G		intron_variant
ABCB1	NM_001348945.2	c.3493-2700T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.3283-2700T>G		intron_variant		1	NM_001348946.2	P1

Frequencies

GnomAD3 genomes AF: 0.565 AC: 84915 AN: 150330 Hom.: 25278 Cov.: 29

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.565 AC: 85022 AN: 150446 Hom.: 25321 Cov.: 29 AF XY: 0.563 AC XY: 41334 AN XY: 73438

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.592

Alfa AF: 0.486 Hom.: 18087

Bravo AF: 0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.16
Dann	Benign	0.81

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: rs1002204; hg19: chr7-87141497;