chr18-74501373-G-A

Position:

• chr18-74501373-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018235.3(CNDP2):​c.105G>A​(p.Pro35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,613,618 control chromosomes in the GnomAD database, including 34,642 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 (3456 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31186 hom.)
• Consequence: CNDP2 NM_018235.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.34

Genes affected

CNDP2 (HGNC:24437): (carnosine dipeptidase 2) CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18), is a nonspecific dipeptidase rather than a selective carnosinase (Teufel et al., 2003 [PubMed 12473676]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-8.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP2	NM_018235.3	c.105G>A	p.Pro35=	synonymous_variant	3/12	ENST00000324262.9	NP_060705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262.9	c.105G>A	p.Pro35=	synonymous_variant	3/12	1	NM_018235.3	ENSP00000325548	P1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31622 AN: 151960 Hom.: 3444 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.214

GnomAD3 exomes AF: 0.218 AC: 54743 AN: 251172 Hom.: 6629 AF XY: 0.216 AC XY: 29294 AN XY: 135756

Gnomad AFR exome AF: 0.226

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.293

Gnomad SAS exome AF: 0.246

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.202 AC: 294983 AN: 1461538 Hom.: 31186 Cov.: 33 AF XY: 0.203 AC XY: 147341 AN XY: 727088

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.208 AC: 31655 AN: 152080 Hom.: 3456 Cov.: 32 AF XY: 0.210 AC XY: 15603 AN XY: 74350

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.214

Alfa AF: 0.194 Hom.: 5785

Bravo AF: 0.220

Asia WGS AF: 0.288 AC: 1004 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.2
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2303463; hg19: chr18-72168608; COSMIC: COSV60838835; COSMIC: COSV60838835;