rs4437575

chr7-87510000-A-G

Variant summary

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

The NM_001348946.2(ABCB1):c.3283-519T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,940 control chromosomes in the GnomAD database, including 14,110 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 0.42 (14110 hom., cov: 31)
• Consequence: ABCB1 NM_001348946.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCB1	NM_001348946.2	c.3283-519T>C		intron_variant		ENST00000622132.5
ABCB1	NM_000927.5	c.3283-519T>C		intron_variant
ABCB1	NM_001348944.2	c.3283-519T>C		intron_variant
ABCB1	NM_001348945.2	c.3493-519T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCB1	ENST00000622132.5	c.3283-519T>C		intron_variant		1	NM_001348946.2	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64494 AN: 151822 Hom.: 14090 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.425 AC: 64554 AN: 151940 Hom.: 14110 Cov.: 31 AF XY: 0.422 AC XY: 31347 AN XY: 74258

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.471

Alfa AF: 0.442 Hom.: 10833

Bravo AF: 0.431

Asia WGS AF: 0.273 AC: 951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.2
Dann	Benign	0.83

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: rs4437575; hg19: chr7-87139316;