rs2292997

Positions:

• chr3-184006284-G-A
• chr3-184006284-G-C
• chr3-184006284-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.129+7980C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 140,368 control chromosomes in the GnomAD database, including 1,336 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 0.13 (1336 hom., cov: 27)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.23

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC5	NM_005688.4	c.129+7980C>T		intron_variant		ENST00000334444.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC5	ENST00000334444.11	c.129+7980C>T		intron_variant		1	NM_005688.4	P1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 18099 AN: 140270 Hom.: 1325 Cov.: 27

Gnomad AFR AF: 0.0887

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0753

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.129 AC: 18127 AN: 140360 Hom.: 1336 Cov.: 27 AF XY: 0.133 AC XY: 8994 AN XY: 67470

Gnomad4 AFR AF: 0.0886

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0778

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.143

Alfa AF: 0.116 Hom.: 1458

Bravo AF: 0.127

Asia WGS AF: 0.239 AC: 831 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2292997; hg19: chr3-183724072;