rs4329999

Positions:

• chr18-74561034-G-A
• chr18-74561034-G-C
• chr18-74561034-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032649.6(CNDP1):​c.466+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 1,607,108 control chromosomes in the GnomAD database, including 63,401 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 0.23 (5049 hom., cov: 31)
  • Exomes 𝑓: 0.28 (58352 hom.)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.17

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.466+16G>A		intron_variant		ENST00000358821.8	NP_116038.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8	c.466+16G>A		intron_variant		1	NM_032649.6	ENSP00000351682.3
CNDP1	ENST00000582365.1	c.337+16G>A		intron_variant		5		ENSP00000462096.1
CNDP1	ENST00000584316.5	n.48+23G>A		intron_variant		4		ENSP00000463807.1
CNDP1	ENST00000585136.1	n.469-1013G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35376 AN: 151880 Hom.: 5047 Cov.: 31

Gnomad AFR AF: 0.0755

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.299 AC: 74499 AN: 249324 Hom.: 12342 AF XY: 0.297 AC XY: 40087 AN XY: 134852

Gnomad AFR exome AF: 0.0744

Gnomad AMR exome AF: 0.446

Gnomad ASJ exome AF: 0.194

Gnomad EAS exome AF: 0.419

Gnomad SAS exome AF: 0.320

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.281

GnomAD4 exome AF: 0.275 AC: 400381 AN: 1455110 Hom.: 58352 Cov.: 34 AF XY: 0.276 AC XY: 199245 AN XY: 722546

Gnomad4 AFR exome AF: 0.0656

Gnomad4 AMR exome AF: 0.434

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.495

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.265

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.233 AC: 35397 AN: 151998 Hom.: 5049 Cov.: 31 AF XY: 0.239 AC XY: 17782 AN XY: 74282

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.440

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.229

Alfa AF: 0.253 Hom.: 5391

Bravo AF: 0.225

Asia WGS AF: 0.380 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.21
DANN	Benign	0.66

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: rs4329999; hg19: chr18-72228269; COSMIC: COSV62594595; COSMIC: COSV62594595;