Genetic Variant CNDP1:p.Asp316Asn (chr18-74576973-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_032649.6(CNDP1):c.946G>A(p.Asp316Asn) variant causes a missense change. The variant allele was found at a frequency of 0.022 in 1,613,270 control chromosomes in the GnomAD database, including 1,361 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.048 ( 349 hom., cov: 32)

Exomes 𝑓: 0.019 ( 1012 hom. )

Consequence

CNDP1
NM_032649.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.78

Publications

14 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:

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=0.0017642379).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNDP1	NM_032649.6 link	c.946G>A	p.Asp316Asn	missense_variant	Exon 8 of 12	ENST00000358821.8	NP_116038.4	Q96KN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8 link	c.946G>A	p.Asp316Asn	missense_variant	Exon 8 of 12	1	NM_032649.6	ENSP00000351682.3		Q96KN2

Frequencies

GnomAD3 genomes

AF:

0.0476

AC:

7246

AN:

152088

Hom.:

349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0470

Gnomad ASJ

AF:

0.0458

Gnomad EAS

AF:

0.0368

Gnomad SAS

AF:

0.0955

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00872

Gnomad OTH

AF:

0.0435

GnomAD2 exomes

AF:

0.0347

AC:

8688

AN:

250732

AF XY:

0.0367

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0282

Gnomad ASJ exome

AF:

0.0472

Gnomad EAS exome

AF:

0.0311

Gnomad FIN exome

AF:

0.00675

Gnomad NFE exome

AF:

0.00994

Gnomad OTH exome

AF:

0.0303

GnomAD4 exome

AF:

0.0193

AC:

28226

AN:

1461064

Hom.:

1012

Cov.:

AF XY:

0.0220

AC XY:

15964

AN XY:

726756

show subpopulations

African (AFR)

AF:

0.116

AC:

3877

AN:

33464

American (AMR)

AF:

0.0308

AC:

1377

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.0479

AC:

1251

AN:

26124

East Asian (EAS)

AF:

0.0348

AC:

1383

AN:

39690

South Asian (SAS)

AF:

0.106

AC:

9086

AN:

85924

European-Finnish (FIN)

AF:

0.00702

AC:

375

AN:

53416

Middle Eastern (MID)

AF:

0.0515

AC:

297

AN:

5764

European-Non Finnish (NFE)

AF:

0.00796

AC:

8850

AN:

1111682

Other (OTH)

AF:

0.0287

AC:

1730

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

1258

2516

3775

5033

6291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.0477

AC:

7257

AN:

152206

Hom.:

349

Cov.:

AF XY:

0.0495

AC XY:

3686

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.120

AC:

4982

AN:

41524

American (AMR)

AF:

0.0468

AC:

715

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

159

AN:

3472

East Asian (EAS)

AF:

0.0367

AC:

190

AN:

5180

South Asian (SAS)

AF:

0.0958

AC:

462

AN:

4824

European-Finnish (FIN)

AF:

0.00538

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00872

AC:

593

AN:

68004

Other (OTH)

AF:

0.0431

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

323

645

968

1290

1613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0204

Hom.:

321

Bravo

AF:

0.0507

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.113

AC:

498

ESP6500EA

AF:

0.0106

AC:

ExAC

AF:

0.0367

AC:

4451

Asia WGS

AF:

0.0640

AC:

221

AN:

3478

EpiCase

AF:

0.0110

EpiControl

AF:

0.0115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.039

Eigen_PC

Benign

0.061

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

.;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

PhyloP100

3.8

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.4

D;.

REVEL

Benign

0.11

Sift

Benign

0.055

T;.

Sift4G

Benign

0.11

T;T

Vest4

0.10

MPC

0.15

ClinPred

0.018

GERP RS

4.2

gMVP

0.72

Mutation Taster

=79/21

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over