rs1144962

Positions:

• chr12-68941205-A-G
• chr12-68941205-A-T

Variant summary

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

The NM_001874.5(CPM):​c.-3-8365T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 141,338 control chromosomes in the GnomAD database, including 12,619 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 0.42 (12619 hom., cov: 24)
• Consequence: CPM NM_001874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPM	NM_001413388.1	c.-132-5234T>C		intron_variant			NP_001400317.1
CPM	NM_001874.5	c.-3-8365T>C		intron_variant			NP_001865.1
CPM	NM_001413393.1	c.-3-8365T>C		intron_variant			NP_001400322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPM	ENST00000546373.5	c.-3-8365T>C		intron_variant		1		ENSP00000447255.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 59321 AN: 141246 Hom.: 12591 Cov.: 24

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.426

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.420 AC: 59385 AN: 141338 Hom.: 12619 Cov.: 24 AF XY: 0.417 AC XY: 28626 AN XY: 68714

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.402

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.426

Alfa AF: 0.392 Hom.: 2476

Bravo AF: 0.439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.27
DANN	Benign	0.41

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: rs1144962; hg19: chr12-69334985; COSMIC: COSV73410103;