rs4148575

Positions:

• chr3-183984487-A-G
• chr3-183984487-A-T

Variant summary

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

The ENST00000427120.6(ABCC5):​c.*3178T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,050,148 control chromosomes in the GnomAD database, including 169,972 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 0.61 (29180 hom., cov: 30)
  • Exomes 𝑓: 0.56 (140792 hom.)
• Consequence: ABCC5 ENST00000427120.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC5	NM_005688.4	c.592-1480T>C		intron_variant		ENST00000334444.11	NP_005679.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC5	ENST00000334444.11	c.592-1480T>C		intron_variant		1	NM_005688.4	ENSP00000333926	P1

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93000 AN: 151760 Hom.: 29151 Cov.: 30

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.625

GnomAD4 exome AF: 0.558 AC: 501038 AN: 898270 Hom.: 140792 Cov.: 34 AF XY: 0.556 AC XY: 233264 AN XY: 419188

Gnomad4 AFR exome AF: 0.734

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.855

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.487

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.613 AC: 93079 AN: 151878 Hom.: 29180 Cov.: 30 AF XY: 0.608 AC XY: 45102 AN XY: 74230

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.588

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.628

Alfa AF: 0.567 Hom.: 49325

Bravo AF: 0.625

Asia WGS AF: 0.709 AC: 2466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.46

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: rs4148575; hg19: chr3-183702275;