rs3741599

Positions:

• chr12-68856701-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_198320.5(CPM):​c.1090-22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,609,374 control chromosomes in the GnomAD database, including 30,277 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.17 (2423 hom., cov: 33)
  • Exomes 𝑓: 0.19 (27854 hom.)
• Consequence: CPM NM_198320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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]

CPM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPM	NM_198320.5	c.1090-22A>G		intron_variant		ENST00000551568.6	NP_938079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPM	ENST00000551568.6	c.1090-22A>G		intron_variant		1	NM_198320.5	ENSP00000448517.1
CPM	ENST00000338356.7	c.1090-22A>G		intron_variant		1		ENSP00000339157.3
CPM	ENST00000546373.5	c.1090-22A>G		intron_variant		1		ENSP00000447255.1
CPM	ENST00000551897.5	c.496-22A>G		intron_variant		5		ENSP00000447455.1

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25706 AN: 152038 Hom.: 2419 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.169 AC: 41938 AN: 248842 Hom.: 4036 AF XY: 0.172 AC XY: 23141 AN XY: 134638

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.210

Gnomad EAS exome AF: 0.0111

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.195

GnomAD4 exome AF: 0.191 AC: 277833 AN: 1457218 Hom.: 27854 Cov.: 33 AF XY: 0.191 AC XY: 138153 AN XY: 724492

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.214

Gnomad4 EAS exome AF: 0.0113

Gnomad4 SAS exome AF: 0.153

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.169 AC: 25725 AN: 152156 Hom.: 2423 Cov.: 33 AF XY: 0.166 AC XY: 12381 AN XY: 74376

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0108

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.208

Alfa AF: 0.194 Hom.: 1142

Bravo AF: 0.170

Asia WGS AF: 0.0670 AC: 231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Benign	0.72
BranchPoint Hunter		3.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: -1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3741599; hg19: chr12-69250481;