rs3749438

Positions:

• chr3-183987396-G-A

Variant summary

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

The ENST00000427120.6(ABCC5):​c.*269C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 469,754 control chromosomes in the GnomAD database, including 31,859 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 0.33 (8632 hom., cov: 32)
  • Exomes 𝑓: 0.38 (23227 hom.)
• Consequence: ABCC5 ENST00000427120.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.591+374C>T		intron_variant		ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.591+374C>T		intron_variant		1	NM_005688.4	ENSP00000333926	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50277 AN: 151776 Hom.: 8635 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.379 AC: 120529 AN: 317860 Hom.: 23227 Cov.: 0 AF XY: 0.381 AC XY: 62517 AN XY: 163968

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.410

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.331 AC: 50275 AN: 151894 Hom.: 8632 Cov.: 32 AF XY: 0.326 AC XY: 24187 AN XY: 74220

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.344

Alfa AF: 0.358 Hom.: 6523

Bravo AF: 0.329

Asia WGS AF: 0.387 AC: 1348 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	0.13
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs3749438; hg19: chr3-183705184;