18-74499889-C-G

Variant names:

• chr18-74499889-C-G
• rs3764509
• NM_018235.3:c.-85C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNDP2	NM_018235.3	c.-85C>G		5_prime_UTR_variant	Exon 2 of 12	ENST00000324262.9	NP_060705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262.9	c.-85C>G		5_prime_UTR_variant	Exon 2 of 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

African (AFR) AF: 0.501 AC: 12553 AN: 25068

American (AMR) AF: 0.376 AC: 12715 AN: 33802

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 4804 AN: 21790

East Asian (EAS) AF: 0.298 AC: 10949 AN: 36778

South Asian (SAS) AF: 0.330 AC: 24215 AN: 73274

European-Finnish (FIN) AF: 0.175 AC: 9096 AN: 51876

Middle Eastern (MID) AF: 0.262 AC: 1300 AN: 4970

European-Non Finnish (NFE) AF: 0.254 AC: 204762 AN: 807488

Other (OTH) AF: 0.267 AC: 12799 AN: 47958

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

African (AFR) AF: 0.494 AC: 20452 AN: 41440

American (AMR) AF: 0.353 AC: 5395 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3468

East Asian (EAS) AF: 0.288 AC: 1490 AN: 5176

South Asian (SAS) AF: 0.338 AC: 1628 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1824 AN: 10602

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16834 AN: 67960

Other (OTH) AF: 0.314 AC: 665 AN: 2116

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
PhyloP100		-2.9
PromoterAI		0.27	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3764509; hg19: chr18-72167124; COSMIC: COSV60840198; COSMIC: COSV60840198;