12-68947245-A-G

Variant summary

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

The ENST00000546373.5(CPM):c.-3-14405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,082 control chromosomes in the GnomAD database, including 8,423 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 0.33 (8423 hom., cov: 32)
• Consequence: CPM ENST00000546373.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPM	NM_001413388.1	c.-132-11274T>C		intron_variant
CPM	NM_001413393.1	c.-3-14405T>C		intron_variant
CPM	NM_001413397.1	c.-397-11274T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPM	ENST00000546373.5	c.-3-14405T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50331 AN: 151964 Hom.: 8411 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.331 AC: 50368 AN: 152082 Hom.: 8423 Cov.: 32 AF XY: 0.331 AC XY: 24643 AN XY: 74348

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.362

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.362

Alfa AF: 0.358 Hom.: 9636

Bravo AF: 0.338

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.11
Dann	Benign	0.68

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: rs1195812; hg19: chr12-69341025;