3-183920057-T-C

Position:

• chr3-183920057-T-C

Variant summary

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

The NM_005688.4(ABCC5):​c.*1243A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,546 control chromosomes in the GnomAD database, including 21,757 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 0.53 (21713 hom., cov: 33)
  • Exomes 𝑓: 0.44 (44 hom.)
• Consequence: ABCC5 NM_005688.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.697

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.*1243A>G		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	ENST00000334444.11	c.*1243A>G		3_prime_UTR_variant	30/30	1	NM_005688.4	ENSP00000333926	P1
ABCC5	ENST00000265586.10	c.*1243A>G		3_prime_UTR_variant	29/29	5		ENSP00000265586
ABCC5	ENST00000437205.5	c.*4250A>G		3_prime_UTR_variant, NMD_transcript_variant	30/30	5		ENSP00000403510

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80027 AN: 151996 Hom.: 21678 Cov.: 33

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.539

GnomAD4 exome AF: 0.440 AC: 190 AN: 432 Hom.: 44 Cov.: 0 AF XY: 0.431 AC XY: 106 AN XY: 246

Gnomad4 FIN exome AF: 0.435

Gnomad4 NFE exome AF: 0.583

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.527 AC: 80112 AN: 152114 Hom.: 21713 Cov.: 33 AF XY: 0.519 AC XY: 38579 AN XY: 74358

Gnomad4 AFR AF: 0.661

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.400

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.543

Alfa AF: 0.490 Hom.: 37932

Bravo AF: 0.538

Asia WGS AF: 0.504 AC: 1756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	13
DANN	Benign	0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs562; hg19: chr3-183637845;