18-74559304-T-C

Position:

• chr18-74559304-T-C

Variant summary

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

The NM_032649.6(CNDP1):​c.154-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 1,613,244 control chromosomes in the GnomAD database, including 506,104 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 (43396 hom., cov: 32)
  • Exomes 𝑓: 0.79 (462708 hom.)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.154-19T>C		intron_variant		ENST00000358821.8	NP_116038.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8	c.154-19T>C		intron_variant		1	NM_032649.6	ENSP00000351682.3
CNDP1	ENST00000582365.1	c.25-19T>C		intron_variant		5		ENSP00000462096.1
CNDP1	ENST00000585136.1	n.319-19T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113474 AN: 151990 Hom.: 43364 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.879

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.764

GnomAD3 exomes AF: 0.806 AC: 202286 AN: 251056 Hom.: 82378 AF XY: 0.804 AC XY: 109139 AN XY: 135718

Gnomad AFR exome AF: 0.574

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.814

Gnomad EAS exome AF: 0.935

Gnomad SAS exome AF: 0.760

Gnomad FIN exome AF: 0.850

Gnomad NFE exome AF: 0.796

Gnomad OTH exome AF: 0.806

GnomAD4 exome AF: 0.794 AC: 1160265 AN: 1461136 Hom.: 462708 Cov.: 40 AF XY: 0.794 AC XY: 576994 AN XY: 726884

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.882

Gnomad4 ASJ exome AF: 0.816

Gnomad4 EAS exome AF: 0.939

Gnomad4 SAS exome AF: 0.757

Gnomad4 FIN exome AF: 0.850

Gnomad4 NFE exome AF: 0.793

Gnomad4 OTH exome AF: 0.786

GnomAD4 genome AF: 0.746 AC: 113548 AN: 152108 Hom.: 43396 Cov.: 32 AF XY: 0.752 AC XY: 55960 AN XY: 74366

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.859

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.766

Alfa AF: 0.743 Hom.: 7609

Bravo AF: 0.738

Asia WGS AF: 0.848 AC: 2948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.13
DANN	Benign	0.39

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: rs12607796; hg19: chr18-72226539;