rs12957330

Positions:

• chr18-74584144-G-A

Variant summary

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

The NM_032649.6(CNDP1):​c.1458-352G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 325,068 control chromosomes in the GnomAD database, including 4,387 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 0.13 (1717 hom., cov: 33)
  • Exomes 𝑓: 0.16 (2670 hom.)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.1458-352G>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.1458-352G>A		intron_variant		1	NM_032649.6	ENSP00000351682	P1
CNDP1	ENST00000582365.1	c.1329-352G>A		intron_variant		5		ENSP00000462096
CNDP1	ENST00000582461.1	n.2774G>A		non_coding_transcript_exon_variant	3/3	5
CNDP1	ENST00000584004.5	n.982-352G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20407 AN: 152074 Hom.: 1719 Cov.: 33

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.164 AC: 28308 AN: 172876 Hom.: 2670 Cov.: 0 AF XY: 0.162 AC XY: 14728 AN XY: 90806

Gnomad4 AFR exome AF: 0.0302

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.0682

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.162

GnomAD4 genome AF: 0.134 AC: 20403 AN: 152192 Hom.: 1717 Cov.: 33 AF XY: 0.133 AC XY: 9923 AN XY: 74410

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.220

Gnomad4 EAS AF: 0.0799

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.128

Alfa AF: 0.180 Hom.: 3264

Bravo AF: 0.127

Asia WGS AF: 0.0940 AC: 328 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	9.5
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs12957330; hg19: chr18-72251380;