Genetic Variant NM_032649.6:c.174C>A (chr18-74559343-C-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_032649.6(CNDP1):c.174C>A(p.Ala58Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,613,966 control chromosomes in the GnomAD database, including 1,441 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 0.058 ( 474 hom., cov: 32)

Exomes 𝑓: 0.029 ( 967 hom. )

Consequence

CNDP1
NM_032649.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.71

Publications

8 publications found

Variant links:

Genes affected

CNDP1 (HGNC:20675): (carnosine dipeptidase 1) This gene encodes a member of the M20 metalloprotease family. The encoded protein is specifically expressed in the brain, is a homodimeric dipeptidase which was identified as human carnosinase. This gene contains trinucleotide (CTG) repeat length polymorphism in the coding region. [provided by RefSeq, Jul 2008]

CNDP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP7

Synonymous conserved (PhyloP=-4.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032649.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	NM_032649.6	MANE Select	c.174C>A	p.Ala58Ala	synonymous	Exon 3 of 12	NP_116038.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNDP1	ENST00000358821.8	TSL:1 MANE Select	c.174C>A	p.Ala58Ala	synonymous	Exon 3 of 12	ENSP00000351682.3	Q96KN2
CNDP1	ENST00000864762.1		c.174C>A	p.Ala58Ala	synonymous	Exon 3 of 12	ENSP00000534821.1
CNDP1	ENST00000954332.1		c.174C>A	p.Ala58Ala	synonymous	Exon 3 of 12	ENSP00000624391.1

Frequencies

GnomAD3 genomes

AF:

0.0584

AC:

8885

AN:

152086

Hom.:

472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.0661

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0267

Gnomad OTH

AF:

0.0556

GnomAD2 exomes

AF:

0.0346

AC:

8691

AN:

251306

AF XY:

0.0324

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.0183

Gnomad ASJ exome

AF:

0.0192

Gnomad EAS exome

AF:

0.0640

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0302

GnomAD4 exome

AF:

0.0294

AC:

42959

AN:

1461762

Hom.:

967

Cov.:

AF XY:

0.0290

AC XY:

21058

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.148

AC:

4953

AN:

33470

American (AMR)

AF:

0.0205

AC:

915

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0191

AC:

499

AN:

26132

East Asian (EAS)

AF:

0.0596

AC:

2366

AN:

39694

South Asian (SAS)

AF:

0.0230

AC:

1981

AN:

86252

European-Finnish (FIN)

AF:

0.0256

AC:

1364

AN:

53366

Middle Eastern (MID)

AF:

0.0345

AC:

199

AN:

5764

European-Non Finnish (NFE)

AF:

0.0256

AC:

28505

AN:

1111970

Other (OTH)

AF:

0.0360

AC:

2177

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2100

4199

6299

8398

10498

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1126

2252

3378

4504

5630

<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:

0.0584

AC:

8895

AN:

152204

Hom.:

474

Cov.:

AF XY:

0.0578

AC XY:

4300

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.137

AC:

5681

AN:

41496

American (AMR)

AF:

0.0343

AC:

525

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3470

East Asian (EAS)

AF:

0.0657

AC:

340

AN:

5176

South Asian (SAS)

AF:

0.0257

AC:

124

AN:

4824

European-Finnish (FIN)

AF:

0.0200

AC:

212

AN:

10622

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0267

AC:

1813

AN:

68016

Other (OTH)

AF:

0.0550

AC:

116

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

405

810

1215

1620

2025

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0382

Hom.:

351

Bravo

AF:

0.0645

Asia WGS

AF:

0.0450

AC:

156

AN:

3478

EpiCase

AF:

0.0267

EpiControl

AF:

0.0235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.7

(source)

DANN

Benign

0.80

PhyloP100

-4.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over