rs12605520

Positions:

• chr18-74559269-C-T

Variant summary

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

The NM_032649.6(CNDP1):​c.154-54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,596,032 control chromosomes in the GnomAD database, including 98,464 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 0.30 (7693 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90771 hom.)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP1	NM_032649.6	c.154-54C>T		intron_variant		ENST00000358821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP1	ENST00000358821.8	c.154-54C>T		intron_variant		1	NM_032649.6	P1
CNDP1	ENST00000582365.1	c.25-54C>T		intron_variant		5
CNDP1	ENST00000585136.1	n.319-54C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45912 AN: 152018 Hom.: 7691 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.351 AC: 506640 AN: 1443896 Hom.: 90771 AF XY: 0.353 AC XY: 254264 AN XY: 719354

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.391

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.302 AC: 45933 AN: 152136 Hom.: 7693 Cov.: 32 AF XY: 0.306 AC XY: 22727 AN XY: 74346

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.352

Alfa AF: 0.357 Hom.: 13094

Bravo AF: 0.295

Asia WGS AF: 0.395 AC: 1370 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.47
DANN	Benign	0.57

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: rs12605520; hg19: chr18-72226504; COSMIC: COSV62593139; COSMIC: COSV62593139;