chr18-74510926-T-C

Position:

• chr18-74510926-T-C

Variant summary

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

The NM_018235.3(CNDP2):​c.570T>C​(p.Tyr190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,812 control chromosomes in the GnomAD database, including 33,025 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 0.18 (2650 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30375 hom.)
• Consequence: CNDP2 NM_018235.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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=-0.66).
• BP7: Synonymous conserved (PhyloP=-0.343 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP2	NM_018235.3	c.570T>C	p.Tyr190=	synonymous_variant	6/12	ENST00000324262.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP2	ENST00000324262.9	c.570T>C	p.Tyr190=	synonymous_variant	6/12	1	NM_018235.3	P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26712 AN: 152096 Hom.: 2642 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.209 AC: 52581 AN: 251452 Hom.: 6211 AF XY: 0.208 AC XY: 28325 AN XY: 135902

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.338

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.297

Gnomad SAS exome AF: 0.232

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.199 AC: 290947 AN: 1461598 Hom.: 30375 Cov.: 34 AF XY: 0.200 AC XY: 145286 AN XY: 727120

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.296

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.176 AC: 26724 AN: 152214 Hom.: 2650 Cov.: 32 AF XY: 0.177 AC XY: 13197 AN XY: 74422

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.185

Alfa AF: 0.187 Hom.: 3550

Bravo AF: 0.184

Asia WGS AF: 0.270 AC: 942 AN: 3478

EpiCase AF: 0.189

EpiControl AF: 0.185

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.5
DANN	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2278159; hg19: chr18-72178161; COSMIC: COSV60839382; COSMIC: COSV60839382;