chr3-183920718-C-T

Position:

• chr3-183920718-C-T

Variant summary

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

The NM_005688.4(ABCC5):​c.*582G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 152,482 control chromosomes in the GnomAD database, including 12,864 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 0.39 (12819 hom., cov: 32)
  • Exomes 𝑓: 0.43 (45 hom.)
• Consequence: ABCC5 NM_005688.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751

Genes affected

ABCC5 (HGNC:56): (ATP binding cassette subfamily C member 5) The 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 MRP subfamily which is involved in multi-drug resistance. This protein functions in the cellular export of its substrate, cyclic nucleotides. This export contributes to the degradation of phosphodiesterases and possibly an elimination pathway for cyclic nucleotides. Studies show that this protein provides resistance to thiopurine anticancer drugs, 6-mercatopurine and thioguanine, and the anti-HIV drug 9-(2-phosphonylmethoxyethyl)adenine. This protein may be involved in resistance to thiopurines in acute lymphoblastic leukemia and antiretroviral nucleoside analogs in HIV-infected patients. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.*582G>A		3_prime_UTR_variant	30/30	ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444	c.*582G>A		3_prime_UTR_variant	30/30	1	NM_005688.4	ENSP00000333926.6
ABCC5	ENST00000265586	c.*582G>A		3_prime_UTR_variant	29/29	5		ENSP00000265586.6
ABCC5	ENST00000437205.5	n.*3589G>A		non_coding_transcript_exon_variant	30/30	5		ENSP00000403510.1
ABCC5	ENST00000437205.5	n.*3589G>A		3_prime_UTR_variant	30/30	5		ENSP00000403510.1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 59011 AN: 151926 Hom.: 12812 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.433 AC: 189 AN: 436 Hom.: 45 Cov.: 0 AF XY: 0.410 AC XY: 109 AN XY: 266

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.388 AC: 59038 AN: 152046 Hom.: 12819 Cov.: 32 AF XY: 0.387 AC XY: 28732 AN XY: 74326

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.435

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.441

Alfa AF: 0.414 Hom.: 1743

Bravo AF: 0.382

Asia WGS AF: 0.471 AC: 1638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.63

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: rs3749445; hg19: chr3-183638506; COSMIC: COSV55590062; COSMIC: COSV55590062;