rs2642556

Positions:

• chr12-68922084-T-C

Variant summary

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

The ENST00000551568.6(CPM):​c.160+10594A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 152,068 control chromosomes in the GnomAD database, including 45,940 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 0.77 (45940 hom., cov: 31)
• Consequence: CPM ENST00000551568.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPM	NM_198320.5	c.160+10594A>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.160+10594A>G		intron_variant		1	NM_198320.5	ENSP00000448517	P1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117575 AN: 151952 Hom.: 45881 Cov.: 31

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.774 AC: 117692 AN: 152068 Hom.: 45940 Cov.: 31 AF XY: 0.768 AC XY: 57102 AN XY: 74336

Gnomad4 AFR AF: 0.894

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.756

Alfa AF: 0.770 Hom.: 7644

Bravo AF: 0.788

Asia WGS AF: 0.674 AC: 2347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.045
DANN	Benign	0.81

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: rs2642556; hg19: chr12-69315864;