rs1144961

chr12-68915597-A-Gchr12-68915597-A-T

Variant summary

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

The NM_198320.5(CPM):c.160+17081T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 152,194 control chromosomes in the GnomAD database, including 46,898 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 0.78 (46898 hom., cov: 33)
• Consequence: CPM NM_198320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPM	NM_198320.5	c.160+17081T>C		intron_variant		ENST00000551568.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPM	ENST00000551568.6	c.160+17081T>C		intron_variant		1	NM_198320.5	P1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118784 AN: 152076 Hom.: 46838 Cov.: 33

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.760

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.656

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.781 AC: 118901 AN: 152194 Hom.: 46898 Cov.: 33 AF XY: 0.775 AC XY: 57612 AN XY: 74368

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.760

Gnomad4 EAS AF: 0.671

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.656

Gnomad4 NFE AF: 0.744

Gnomad4 OTH AF: 0.762

Alfa AF: 0.743 Hom.: 19417

Bravo AF: 0.796

Asia WGS AF: 0.677 AC: 2358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	3.6
Dann	Benign	0.69

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: rs1144961; hg19: chr12-69309377;