Variant 18-74556378-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032649.6(CNDP1):c.65G>A(p.Arg22His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,558,530 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

CNDP1
NM_032649.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.120

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0067830086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP1	NM_032649.6 link	c.65G>A	p.Arg22His	missense_variant	2/12	ENST00000358821.8	NP_116038.4	Q96KN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CNDP1	ENST00000358821.8 link	c.65G>A	p.Arg22His	missense_variant	2/12	1	NM_032649.6	ENSP00000351682.3	Q96KN2
CNDP1	ENST00000582365.1 link	c.25-2945G>A		intron_variant		5		ENSP00000462096.1	J3KRP0
CNDP1	ENST00000585136.1 link	n.230G>A		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.000973

AC:

144

AN:

147974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000519

Gnomad AMI

AF:

0.0156

Gnomad AMR

AF:

0.000205

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000207

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000573

AC:

143

AN:

249404

Hom.:

AF XY:

0.000600

AC XY:

AN XY:

134902

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00115

Gnomad OTH exome

AF:

0.000821

GnomAD4 exome

AF:

0.00123

AC:

1739

AN:

1410452

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

845

AN XY:

703334

show subpopulations

Gnomad4 AFR exome

AF:

0.000486

Gnomad4 AMR exome

AF:

0.000293

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000586

Gnomad4 FIN exome

AF:

0.0000569

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000972

AC:

144

AN:

148078

Hom.:

Cov.:

AF XY:

0.000858

AC XY:

AN XY:

72232

show subpopulations

Gnomad4 AFR

AF:

0.000518

Gnomad4 AMR

AF:

0.000205

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000208

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000982

Hom.:

Bravo

AF:

0.00100

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000527

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 28, 2024

The c.65G>A (p.R22H) alteration is located in exon 2 (coding exon 2) of the CNDP1 gene. This alteration results from a G to A substitution at nucleotide position 65, causing the arginine (R) at amino acid position 22 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.8

DANN

Benign

0.74

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.094

M_CAP

Benign

0.0053

MetaRNN

Benign

0.0068

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.21

REVEL

Benign

0.096

Sift

Benign

0.53

Sift4G

Benign

0.55

Vest4

0.20

MVP

0.20

MPC

0.21

ClinPred

0.019

GERP RS

4.0

gMVP

0.28

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over