rs2647952

chr12-68925483-G-Achr12-68925483-G-C

Variant summary

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

The NM_198320.5(CPM):c.160+7195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,138 control chromosomes in the GnomAD database, including 45,311 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 (45311 hom., cov: 33)
• Consequence: CPM NM_198320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPM	NM_198320.5	c.160+7195C>T		intron_variant		ENST00000551568.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPM	ENST00000551568.6	c.160+7195C>T		intron_variant		1	NM_198320.5	P1

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116930 AN: 152020 Hom.: 45262 Cov.: 33

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.769 AC: 117034 AN: 152138 Hom.: 45311 Cov.: 33 AF XY: 0.763 AC XY: 56755 AN XY: 74360

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.658

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.750

Alfa AF: 0.764 Hom.: 7191

Bravo AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	3.5
Dann	Benign	0.46

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: rs2647952; hg19: chr12-69319263;