12-68941205-A-G

Variant names:

• chr12-68941205-A-G
• rs1144962
• ENST00000546373.5:c.-3-8365T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000546373.5(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 ENST00000546373.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CPM	NM_001413388.1	c.-132-5234T>C		intron_variant	Intron 1 of 9		NP_001400317.1
CPM	NM_001874.5	c.-3-8365T>C		intron_variant	Intron 1 of 8		NP_001865.1
CPM	NM_001413393.1	c.-3-8365T>C		intron_variant	Intron 1 of 7		NP_001400322.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPM	ENST00000546373.5	c.-3-8365T>C		intron_variant	Intron 1 of 8	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

African (AFR) AF: 0.581 AC: 20912 AN: 36016

American (AMR) AF: 0.402 AC: 5732 AN: 14242

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1708 AN: 3346

East Asian (EAS) AF: 0.375 AC: 1805 AN: 4814

South Asian (SAS) AF: 0.480 AC: 2098 AN: 4370

European-Finnish (FIN) AF: 0.272 AC: 2660 AN: 9776

Middle Eastern (MID) AF: 0.407 AC: 109 AN: 268

European-Non Finnish (NFE) AF: 0.354 AC: 23263 AN: 65694

Other (OTH) AF: 0.426 AC: 825 AN: 1938

Alfa AF: 0.384 Hom.: 15906

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
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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