12-68947245-A-G

Variant names:

• chr12-68947245-A-G
• rs1195812
• ENST00000546373.5:c.-3-14405T>C

Variant summary

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

The NM_001874.5(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 NM_001874.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001874.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPM	NM_001413388.1		c.-132-11274T>C		intron	N/A	NP_001400317.1	P14384
	CPM	NM_001874.5		c.-3-14405T>C		intron	N/A	NP_001865.1	P14384
	CPM	NM_001413393.1		c.-3-14405T>C		intron	N/A	NP_001400322.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPM	ENST00000546373.5	TSL:1	c.-3-14405T>C		intron	N/A	ENSP00000447255.1	P14384
	CPM	ENST00000961569.1		c.-132-11274T>C		intron	N/A	ENSP00000631628.1

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

African (AFR) AF: 0.268 AC: 11112 AN: 41500

American (AMR) AF: 0.361 AC: 5513 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1637 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1870 AN: 5164

South Asian (SAS) AF: 0.458 AC: 2206 AN: 4818

European-Finnish (FIN) AF: 0.282 AC: 2983 AN: 10566

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23878 AN: 67968

Other (OTH) AF: 0.362 AC: 766 AN: 2114

Alfa AF: 0.355 Hom.: 12292

Bravo AF: 0.338

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.68
PhyloP100		-0.83
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: rs1195812; hg19: chr12-69341025;