rs10248420

Positions:

• chr7-87535670-A-G
• chr7-87535670-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.2481+788T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,084 control chromosomes in the GnomAD database, including 7,040 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 0.27 (7040 hom., cov: 32)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.2481+788T>C		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.2481+788T>C		intron_variant
ABCB1	NM_001348944.2	c.2481+788T>C		intron_variant
ABCB1	NM_001348945.2	c.2691+788T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.2481+788T>C		intron_variant		1	NM_001348946.2	P1
ABCB1	ENST00000265724.8	c.2481+788T>C		intron_variant		1		P1
ABCB1	ENST00000543898.5	c.2289+788T>C		intron_variant		5
ABCB1	ENST00000496821.5	n.109+788T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40547 AN: 151966 Hom.: 7014 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.267 AC: 40629 AN: 152084 Hom.: 7040 Cov.: 32 AF XY: 0.266 AC XY: 19745 AN XY: 74364

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.252

Alfa AF: 0.189 Hom.: 5047

Bravo AF: 0.288

Asia WGS AF: 0.335 AC: 1162 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.64
DANN	Benign	0.56

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: rs10248420; hg19: chr7-87164986;