rs2313212

Positions:

• chr3-183983140-A-G
• chr3-183983140-A-T

Variant summary

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

The NM_005688.4(ABCC5):​c.592-133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 773,806 control chromosomes in the GnomAD database, including 134,717 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 0.62 (30462 hom., cov: 33)
  • Exomes 𝑓: 0.57 (104255 hom.)
• Consequence: ABCC5 NM_005688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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=-0.92).
• 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	UniProt
ABCC5	NM_005688.4	c.592-133T>C		intron_variant		ENST00000334444.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC5	ENST00000334444.11	c.592-133T>C		intron_variant		1	NM_005688.4	P1
ABCC5	ENST00000265586.10	c.592-133T>C		intron_variant		5
ABCC5	ENST00000437205.5	c.592-133T>C		intron_variant, NMD_transcript_variant		5
ABCC5	ENST00000492216.1	n.143-133T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94781 AN: 152052 Hom.: 30418 Cov.: 33

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.573 AC: 356042 AN: 621636 Hom.: 104255 AF XY: 0.571 AC XY: 183795 AN XY: 321948

Gnomad4 AFR exome AF: 0.766

Gnomad4 AMR exome AF: 0.546

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.554

Gnomad4 OTH exome AF: 0.581

GnomAD4 genome AF: 0.623 AC: 94876 AN: 152170 Hom.: 30462 Cov.: 33 AF XY: 0.618 AC XY: 45939 AN XY: 74384

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.558

Gnomad4 OTH AF: 0.637

Alfa AF: 0.569 Hom.: 49969

Bravo AF: 0.635

Asia WGS AF: 0.725 AC: 2523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.47

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: rs2313212; hg19: chr3-183700928;