rs13486

Positions:

• chr12-68855307-A-G

Variant summary

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

The NM_198320.5(CPM):​c.*1130T>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 0.195 in 152,156 control chromosomes in the GnomAD database, including 3,092 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 0.19 (3084 hom., cov: 31)
  • Exomes 𝑓: 0.21 (8 hom.)
• Consequence: CPM NM_198320.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

Genes affected

CPM (HGNC:2311): (carboxypeptidase M) The protein encoded by this gene is a membrane-bound arginine/lysine carboxypeptidase. Its expression is associated with monocyte to macrophage differentiation. This encoded protein contains hydrophobic regions at the amino and carboxy termini and has 6 potential asparagine-linked glycosylation sites. The active site residues of carboxypeptidases A and B are conserved in this protein. Three alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPM	NM_198320.5	c.*1130T>C		3_prime_UTR_variant	9/9	ENST00000551568.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPM	ENST00000551568.6	c.*1130T>C		3_prime_UTR_variant	9/9	1	NM_198320.5	P1
CPM	ENST00000338356.7	c.*1130T>C		3_prime_UTR_variant	8/8	1		P1
CPM	ENST00000551897.5	c.533+1337T>C		intron_variant		5
CPM	ENST00000546556.1	c.*456+674T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29542 AN: 151892 Hom.: 3080 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.212 AC: 31 AN: 146 Hom.: 8 Cov.: 0 AF XY: 0.219 AC XY: 21 AN XY: 96

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.195 AC: 29573 AN: 152010 Hom.: 3084 Cov.: 31 AF XY: 0.191 AC XY: 14165 AN XY: 74296

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.0102

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.229

Alfa AF: 0.212 Hom.: 1552

Bravo AF: 0.195

Asia WGS AF: 0.0690 AC: 239 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.0
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13486; hg19: chr12-69249087;