18-74556352-G-GGCTGT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_032649.6(CNDP1):c.44_48dup(p.Leu17CysfsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00184 in 1,582,764 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (1 hom.)
• Consequence: CNDP1 NM_032649.6 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.954

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 18-74556352-G-GGCTGT is Benign according to our data. Variant chr18-74556352-G-GGCTGT is described in ClinVar as [Likely_benign]. Clinvar id is 3033283.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP1	NM_032649.6	c.44_48dup	p.Leu17CysfsTer21	frameshift_variant	2/12	ENST00000358821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP1	ENST00000358821.8	c.44_48dup	p.Leu17CysfsTer21	frameshift_variant	2/12	1	NM_032649.6	P1
CNDP1	ENST00000582365.1	c.25-2966_25-2962dup		intron_variant		5
CNDP1	ENST00000585136.1	n.209_213dup		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 205 AN: 126276 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.0216

Gnomad AMR AF: 0.000272

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000439

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00270

Gnomad OTH AF: 0.000580

GnomAD3 exomes AF: 0.00143 AC: 320 AN: 223164 Hom.: 0 AF XY: 0.00143 AC XY: 175 AN XY: 122192

Gnomad AFR exome AF: 0.000259

Gnomad AMR exome AF: 0.000243

Gnomad ASJ exome AF: 0.000215

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000590

Gnomad NFE exome AF: 0.00269

Gnomad OTH exome AF: 0.000726

GnomAD4 exome AF: 0.00186 AC: 2706 AN: 1456394 Hom.: 1 Cov.: 30 AF XY: 0.00178 AC XY: 1293 AN XY: 724522

Gnomad4 AFR exome AF: 0.000180

Gnomad4 AMR exome AF: 0.000227

Gnomad4 ASJ exome AF: 0.000154

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000772

Gnomad4 NFE exome AF: 0.00232

Gnomad4 OTH exome AF: 0.00115

GnomAD4 genome AF: 0.00161 AC: 204 AN: 126370 Hom.: 0 Cov.: 33 AF XY: 0.00123 AC XY: 75 AN XY: 61140

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.000272

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000439

Gnomad4 NFE AF: 0.00268

Gnomad4 OTH AF: 0.000575

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.00131

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CNDP1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 17, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs532358622; hg19: chr18-72223587;