12-68909484-T-G

Variant names:

• chr12-68909484-T-G
• rs1152934
• NM_198320.5:c.160+23194A>C

Variant summary

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

The NM_198320.5(CPM):​c.160+23194A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.653 in 151,980 control chromosomes in the GnomAD database, including 32,342 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 0.65 (32342 hom., cov: 30)
• Consequence: CPM NM_198320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPM	NM_198320.5	c.160+23194A>C		intron_variant	Intron 2 of 8	ENST00000551568.6	NP_938079.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPM	ENST00000551568.6	c.160+23194A>C		intron_variant	Intron 2 of 8	1	NM_198320.5	ENSP00000448517.1

Frequencies

GnomAD3 genomes AF: 0.653 AC: 99155 AN: 151862 Hom.: 32315 Cov.: 30

Gnomad AFR AF: 0.657

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.653 AC: 99238 AN: 151980 Hom.: 32342 Cov.: 30 AF XY: 0.648 AC XY: 48118 AN XY: 74270

African (AFR) AF: 0.657 AC: 27218 AN: 41448

American (AMR) AF: 0.668 AC: 10214 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2270 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3103 AN: 5164

South Asian (SAS) AF: 0.665 AC: 3207 AN: 4826

European-Finnish (FIN) AF: 0.573 AC: 6032 AN: 10528

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45064 AN: 67950

Other (OTH) AF: 0.667 AC: 1403 AN: 2104

Alfa AF: 0.659 Hom.: 15668

Bravo AF: 0.664

Asia WGS AF: 0.594 AC: 2066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.7
DANN	Benign	0.67
PhyloP100		0.53
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: rs1152934; hg19: chr12-69303264;