chr18-74567400-C-T

Variant names:

• chr18-74567400-C-T
• rs12960862
• NM_032649.6:c.723C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032649.6(CNDP1):​c.723C>T​(p.Tyr241Tyr) 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
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	NM_032649.6	MANE Select	c.723C>T	p.Tyr241Tyr	synonymous	Exon 6 of 12	NP_116038.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	ENST00000358821.8	TSL:1 MANE Select	c.723C>T	p.Tyr241Tyr	synonymous	Exon 6 of 12	ENSP00000351682.3
	CNDP1	ENST00000864762.1		c.723C>T	p.Tyr241Tyr	synonymous	Exon 6 of 12	ENSP00000534821.1
	CNDP1	ENST00000954332.1		c.723C>T	p.Tyr241Tyr	synonymous	Exon 6 of 12	ENSP00000624391.1

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

GnomAD2 exomes AF: 0.591 AC: 148375 AN: 251260 AF XY: 0.595

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 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

African (AFR) AF: 0.334 AC: 11165 AN: 33464

American (AMR) AF: 0.551 AC: 24647 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 16638 AN: 26126

East Asian (EAS) AF: 0.369 AC: 14649 AN: 39698

South Asian (SAS) AF: 0.532 AC: 45844 AN: 86236

European-Finnish (FIN) AF: 0.666 AC: 35560 AN: 53416

Middle Eastern (MID) AF: 0.605 AC: 3489 AN: 5766

European-Non Finnish (NFE) AF: 0.676 AC: 751669 AN: 1111370

Other (OTH) AF: 0.615 AC: 37106 AN: 60360

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

African (AFR) AF: 0.349 AC: 14458 AN: 41460

American (AMR) AF: 0.547 AC: 8359 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2172 AN: 3468

East Asian (EAS) AF: 0.408 AC: 2106 AN: 5166

South Asian (SAS) AF: 0.520 AC: 2502 AN: 4812

European-Finnish (FIN) AF: 0.657 AC: 6955 AN: 10578

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45402 AN: 67984

Other (OTH) AF: 0.579 AC: 1223 AN: 2112

Alfa AF: 0.632 Hom.: 137339

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.015
DANN	Benign	0.26
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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