rs1914525

Positions:

• chr10-123786120-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CPXM2	NM_198148.3	c.890-5865G>A		intron_variant		ENST00000241305.4	NP_937791.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CPXM2	ENST00000241305.4	c.890-5865G>A		intron_variant		1	NM_198148.3	ENSP00000241305	P1
CPXM2	ENST00000615851.4	c.-623-5865G>A		intron_variant		5		ENSP00000483180
CPXM2	ENST00000368854.7	n.760-5865G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0714

Gnomad4 EAS AF: 0.0397

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.196

Alfa AF: 0.161 Hom.: 1383

Bravo AF: 0.221

Asia WGS AF: 0.113 AC: 391 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	1.0
DANN	Benign	0.58

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: rs1914525; hg19: chr10-125545636;