rs2235048

Positions:

• chr7-87509195-G-A
• chr7-87509195-G-C

Variant summary

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

The NM_001348946.2(ABCB1):​c.3489+80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,435,846 control chromosomes in the GnomAD database, including 174,173 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 (26515 hom., cov: 31)
  • Exomes 𝑓: 0.47 (147658 hom.)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.833

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.3489+80C>T		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.3489+80C>T		intron_variant
ABCB1	NM_001348944.2	c.3489+80C>T		intron_variant
ABCB1	NM_001348945.2	c.3699+80C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.3489+80C>T		intron_variant		1	NM_001348946.2	P1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86593 AN: 151916 Hom.: 26459 Cov.: 31

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.596

GnomAD4 exome AF: 0.472 AC: 605993 AN: 1283812 Hom.: 147658 AF XY: 0.468 AC XY: 303111 AN XY: 647248

Gnomad4 AFR exome AF: 0.817

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.600

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.570 AC: 86711 AN: 152034 Hom.: 26515 Cov.: 31 AF XY: 0.567 AC XY: 42128 AN XY: 74302

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.595

Alfa AF: 0.502 Hom.: 14486

Bravo AF: 0.597

Asia WGS AF: 0.515 AC: 1791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.36

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: rs2235048; hg19: chr7-87138511;