rs1016752

Positions:

• chr3-183947274-G-C
• chr3-183947274-G-T

Variant summary

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

The NM_005688.4(ABCC5):​c.3414+50C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,508,722 control chromosomes in the GnomAD database, including 317,560 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 0.71 (40056 hom., cov: 30)
  • Exomes 𝑓: 0.63 (277504 hom.)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.3414+50C>G		intron_variant		ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.3414+50C>G		intron_variant		1	NM_005688.4	ENSP00000333926.6
ABCC5	ENST00000265586.10	c.3285+50C>G		intron_variant		5		ENSP00000265586.6
ABCC5	ENST00000437205.5	n.*2107+50C>G		intron_variant		5		ENSP00000403510.1

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108293 AN: 151638 Hom.: 40001 Cov.: 30

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.724

GnomAD3 exomes AF: 0.669 AC: 113269 AN: 169422 Hom.: 38851 AF XY: 0.657 AC XY: 59906 AN XY: 91178

Gnomad AFR exome AF: 0.912

Gnomad AMR exome AF: 0.670

Gnomad ASJ exome AF: 0.718

Gnomad EAS exome AF: 0.923

Gnomad SAS exome AF: 0.599

Gnomad FIN exome AF: 0.551

Gnomad NFE exome AF: 0.626

Gnomad OTH exome AF: 0.673

GnomAD4 exome AF: 0.635 AC: 861524 AN: 1356966 Hom.: 277504 Cov.: 25 AF XY: 0.633 AC XY: 420696 AN XY: 664572

Gnomad4 AFR exome AF: 0.913

Gnomad4 AMR exome AF: 0.677

Gnomad4 ASJ exome AF: 0.720

Gnomad4 EAS exome AF: 0.933

Gnomad4 SAS exome AF: 0.588

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.619

Gnomad4 OTH exome AF: 0.656

GnomAD4 genome AF: 0.714 AC: 108407 AN: 151756 Hom.: 40056 Cov.: 30 AF XY: 0.708 AC XY: 52464 AN XY: 74130

Gnomad4 AFR AF: 0.901

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.624

Gnomad4 OTH AF: 0.729

Alfa AF: 0.664 Hom.: 6325

Bravo AF: 0.737

Asia WGS AF: 0.783 AC: 2727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.021
DANN	Benign	0.36
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: rs1016752; hg19: chr3-183665062; COSMIC: COSV55586874; COSMIC: COSV55586874;