10-123786120-C-T

Variant names:

• chr10-123786120-C-T
• rs1914525
• NM_198148.3:c.890-5865G>A

Variant summary

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

The NM_198148.3(CPXM2):​c.890-5865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,204 control chromosomes in the GnomAD database, including 4,700 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 0.21 (4700 hom., cov: 33)
• Consequence: CPXM2 NM_198148.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 2 publications found

Genes affected

CPXM2 (HGNC:26977): (carboxypeptidase X, M14 family member 2) Predicted to enable metallocarboxypeptidase activity. Predicted to be involved in peptide metabolic process and protein processing. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

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 (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198148.3. 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
	CPXM2	NM_198148.3	MANE Select	c.890-5865G>A		intron	N/A	NP_937791.2	Q8N436

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPXM2	ENST00000241305.4	TSL:1 MANE Select	c.890-5865G>A		intron	N/A	ENSP00000241305.3	Q8N436
	CPXM2	ENST00000909350.1		c.887-5865G>A		intron	N/A	ENSP00000579409.1
	CPXM2	ENST00000909348.1		c.791-5865G>A		intron	N/A	ENSP00000579407.1

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32523 AN: 152084 Hom.: 4689 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0714

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.144

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.214 AC: 32558 AN: 152204 Hom.: 4700 Cov.: 33 AF XY: 0.208 AC XY: 15510 AN XY: 74394

African (AFR) AF: 0.416 AC: 17270 AN: 41514

American (AMR) AF: 0.129 AC: 1977 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0714 AC: 248 AN: 3472

East Asian (EAS) AF: 0.0397 AC: 206 AN: 5184

South Asian (SAS) AF: 0.141 AC: 682 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1561 AN: 10596

Middle Eastern (MID) AF: 0.145 AC: 42 AN: 290

European-Non Finnish (NFE) AF: 0.146 AC: 9937 AN: 68004

Other (OTH) AF: 0.196 AC: 414 AN: 2114

Alfa AF: 0.171 Hom.: 5456

Bravo AF: 0.221

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.0
DANN	Benign	0.58
PhyloP100		-0.48
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: rs1914525; hg19: chr10-125545636;