chr18-74567400-C-T

Position:

• chr18-74567400-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032649.6(CNDP1):​c.723C>T​(p.Tyr241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 1,613,224 control chromosomes in the GnomAD database, including 332,887 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 0.55 (24682 hom., cov: 32)
  • Exomes 𝑓: 0.64 (308205 hom.)
• Consequence: CNDP1 NM_032649.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.781

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.781 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.723C>T	p.Tyr241=	synonymous_variant	6/12	ENST00000358821.8	NP_116038.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8	c.723C>T	p.Tyr241=	synonymous_variant	6/12	1	NM_032649.6	ENSP00000351682	P1
CNDP1	ENST00000582365.1	c.594C>T	p.Tyr198=	synonymous_variant	5/11	5		ENSP00000462096
CNDP1	ENST00000584004.5	n.247C>T		non_coding_transcript_exon_variant	1/7	2
CNDP1	ENST00000584316.5	c.*191C>T		3_prime_UTR_variant, NMD_transcript_variant	3/5	4		ENSP00000463807

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83999 AN: 151952 Hom.: 24678 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.579

GnomAD3 exomes AF: 0.591 AC: 148375 AN: 251260 Hom.: 45340 AF XY: 0.595 AC XY: 80763 AN XY: 135798

Gnomad AFR exome AF: 0.342

Gnomad AMR exome AF: 0.550

Gnomad ASJ exome AF: 0.637

Gnomad EAS exome AF: 0.425

Gnomad SAS exome AF: 0.525

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.663

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.644 AC: 940767 AN: 1461154 Hom.: 308205 Cov.: 49 AF XY: 0.641 AC XY: 465955 AN XY: 726924

Gnomad4 AFR exome AF: 0.334

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.637

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.666

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.552 AC: 84014 AN: 152070 Hom.: 24682 Cov.: 32 AF XY: 0.550 AC XY: 40872 AN XY: 74326

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.579

Alfa AF: 0.642 Hom.: 74309

Bravo AF: 0.537

Asia WGS AF: 0.455 AC: 1580 AN: 3478

EpiCase AF: 0.668

EpiControl AF: 0.668

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.015
DANN	Benign	0.26

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

Other links and lift over

dbSNP: rs12960862; hg19: chr18-72234635; COSMIC: COSV62595841; COSMIC: COSV62595841;