Genetic Variant NM_018235.3:c.376T>C (chr18-74508848-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.65

Publications

50 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.376T>C	p.Tyr126His	missense_variant	Exon 5 of 12	ENST00000324262.9	NP_060705.2	Q96KP4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262.9 link	c.376T>C	p.Tyr126His	missense_variant	Exon 5 of 12	1	NM_018235.3	ENSP00000325548.4		Q96KP4-1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29934

AN:

151916

Hom.:

3279

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.231

AC XY:

168032

AN XY:

726654

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

12016

24032

36049

48065

60081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9058

18116

27174

36232

45290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.197

AC:

29947

AN:

152034

Hom.:

3288

Cov.:

AF XY:

0.198

AC XY:

14713

AN XY:

74332

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.224

AC:

15252

AN:

67976

Other (OTH)

AF:

0.207

AC:

438

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1216

2431

3647

4862

6078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

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

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

MutationAssessor

Pathogenic

3.1

.;M;.;M;.;.;.;.;.;.

PhyloP100

7.7

PrimateAI

Uncertain

0.72

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

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)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over