chr18-74508848-T-C

Variant names:

• chr18-74508848-T-C
• rs2278161
• NM_018235.3:c.376T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018235.3(CNDP2):​c.376T>C​(p.Tyr126His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,612,658 control chromosomes in the GnomAD database, including 43,585 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 0.20 (3288 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40297 hom.)
• Consequence: CNDP2 NM_018235.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.65
• Publications: 50 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 (MetaRNN=0.002690345).
• 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 rank	MANE	Protein	UniProt
CNDP2	NM_018235.3	c.376T>C	p.Tyr126His	missense_variant	Exon 5 of 12	ENST00000324262.9	NP_060705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262.9	c.376T>C	p.Tyr126His	missense_variant	Exon 5 of 12	1	NM_018235.3	ENSP00000325548.4

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29934 AN: 151916 Hom.: 3279 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.208

GnomAD2 exomes AF: 0.232 AC: 58365 AN: 251346 AF XY: 0.232

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.350

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.299

Gnomad FIN exome AF: 0.134

Gnomad NFE exome AF: 0.220

Gnomad OTH exome AF: 0.221

GnomAD4 exome AF: 0.231 AC: 336772 AN: 1460624 Hom.: 40297 Cov.: 31 AF XY: 0.231 AC XY: 168032 AN XY: 726654

African (AFR) AF: 0.112 AC: 3731 AN: 33454

American (AMR) AF: 0.347 AC: 15501 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4274 AN: 26132

East Asian (EAS) AF: 0.300 AC: 11920 AN: 39686

South Asian (SAS) AF: 0.258 AC: 22266 AN: 86226

European-Finnish (FIN) AF: 0.140 AC: 7471 AN: 53414

Middle Eastern (MID) AF: 0.195 AC: 1121 AN: 5762

European-Non Finnish (NFE) AF: 0.232 AC: 257584 AN: 1110874

Other (OTH) AF: 0.214 AC: 12904 AN: 60362

GnomAD4 genome AF: 0.197 AC: 29947 AN: 152034 Hom.: 3288 Cov.: 32 AF XY: 0.198 AC XY: 14713 AN XY: 74332

African (AFR) AF: 0.114 AC: 4738 AN: 41460

American (AMR) AF: 0.292 AC: 4464 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1500 AN: 5160

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4806

European-Finnish (FIN) AF: 0.133 AC: 1409 AN: 10582

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15252 AN: 67976

Other (OTH) AF: 0.207 AC: 438 AN: 2116

Alfa AF: 0.218 Hom.: 16916

Bravo AF: 0.204

TwinsUK AF: 0.240 AC: 891

ALSPAC AF: 0.230 AC: 888

ESP6500AA AF: 0.118 AC: 521

ESP6500EA AF: 0.223 AC: 1919

ExAC AF: 0.227 AC: 27504

Asia WGS AF: 0.284 AC: 990 AN: 3478

EpiCase AF: 0.219

EpiControl AF: 0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.23	T;T;.;T;T;T;T;.;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T;.;T;T;T;D;T;T;T;T
MetaRNN	Benign	0.0027	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	.;M;.;M;.;.;.;.;.;.
PhyloP100		7.7
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.3	.;D;.;.;.;.;.;.;.;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.0070	.;D;.;.;.;.;.;.;.;.
Sift4G	Uncertain	0.0040	D;D;D;D;D;D;D;D;D;D
Polyphen		0.54	.;P;.;P;.;.;.;.;.;.
Vest4		0.31, 0.31, 0.64
MPC		0.47
ClinPred		0.032	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.90
Mutation Taster		=84/16	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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: rs2278161; hg19: chr18-72176083; COSMIC: COSV60839006; COSMIC: COSV60839006;