chr12-68889207-T-G

Position:

• chr12-68889207-T-G

Variant summary

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

The NM_198320.5(CPM):​c.161-3318A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,980 control chromosomes in the GnomAD database, including 19,908 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 0.50 (19908 hom., cov: 32)
• Consequence: CPM NM_198320.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306

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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPM	NM_198320.5	c.161-3318A>C		intron_variant		ENST00000551568.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPM	ENST00000551568.6	c.161-3318A>C		intron_variant		1	NM_198320.5	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76207 AN: 151862 Hom.: 19901 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.507

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.502 AC: 76221 AN: 151980 Hom.: 19908 Cov.: 32 AF XY: 0.498 AC XY: 37004 AN XY: 74264

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.522

Alfa AF: 0.532 Hom.: 3358

Bravo AF: 0.493

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.84

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: rs1532328; hg19: chr12-69282987;