rs12605490

chr18-74559220-A-T

Variant summary

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

The NM_032649.6(CNDP1):c.154-103A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,172,228 control chromosomes in the GnomAD database, including 363,163 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 0.75 (43387 hom., cov: 31)
  • Exomes 𝑓: 0.79 (319776 hom.)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP1	NM_032649.6	c.154-103A>T		intron_variant		ENST00000358821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP1	ENST00000358821.8	c.154-103A>T		intron_variant		1	NM_032649.6	P1
CNDP1	ENST00000582365.1	c.25-103A>T		intron_variant		5
CNDP1	ENST00000585136.1	n.319-103A>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113433 AN: 151910 Hom.: 43357 Cov.: 31

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.767

GnomAD4 exome AF: 0.790 AC: 805679 AN: 1020200 Hom.: 319776 AF XY: 0.790 AC XY: 415610 AN XY: 526416

Gnomad4 AFR exome AF: 0.559

Gnomad4 AMR exome AF: 0.882

Gnomad4 ASJ exome AF: 0.815

Gnomad4 EAS exome AF: 0.940

Gnomad4 SAS exome AF: 0.756

Gnomad4 FIN exome AF: 0.848

Gnomad4 NFE exome AF: 0.784

Gnomad4 OTH exome AF: 0.782

GnomAD4 genome AF: 0.747 AC: 113504 AN: 152028 Hom.: 43387 Cov.: 31 AF XY: 0.753 AC XY: 55939 AN XY: 74322

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.769

Alfa AF: 0.763 Hom.: 5536

Bravo AF: 0.738

Asia WGS AF: 0.849 AC: 2951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.63
Dann	Benign	0.54

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: rs12605490; hg19: chr18-72226455; COSMIC: COSV62593480; COSMIC: COSV62593480;