18-74499889-C-G

Position:

• chr18-74499889-C-G

Variant summary

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

The NM_018235.3(CNDP2):​c.-85C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,255,076 control chromosomes in the GnomAD database, including 49,791 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 0.32 (8994 hom., cov: 32)
  • Exomes 𝑓: 0.27 (40797 hom.)
• Consequence: CNDP2 NM_018235.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95

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]

CNDP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP2	NM_018235.3	c.-85C>G		5_prime_UTR_variant	2/12	ENST00000324262.9	NP_060705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262	c.-85C>G		5_prime_UTR_variant	2/12	1	NM_018235.3	ENSP00000325548.4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49335 AN: 151954 Hom.: 8978 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.315

GnomAD4 exome AF: 0.266 AC: 293193 AN: 1103004 Hom.: 40797 Cov.: 13 AF XY: 0.267 AC XY: 150336 AN XY: 562738

Gnomad4 AFR exome AF: 0.501

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.298

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.267

GnomAD4 genome AF: 0.325 AC: 49386 AN: 152072 Hom.: 8994 Cov.: 32 AF XY: 0.324 AC XY: 24079 AN XY: 74334

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.314

Alfa AF: 0.147 Hom.: 250

Bravo AF: 0.344

Asia WGS AF: 0.343 AC: 1195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3764509; hg19: chr18-72167124; COSMIC: COSV60840198; COSMIC: COSV60840198;