18-74578846-T-C

Variant names:

• chr18-74578846-T-C
• rs7229005
• NM_032649.6:c.1167+519T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032649.6(CNDP1):​c.1167+519T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,124 control chromosomes in the GnomAD database, including 3,937 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 (3937 hom., cov: 31)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.1167+519T>C		intron_variant	Intron 9 of 11	ENST00000358821.8	NP_116038.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8	c.1167+519T>C		intron_variant	Intron 9 of 11	1	NM_032649.6	ENSP00000351682.3
CNDP1	ENST00000582365.1	c.1038+519T>C		intron_variant	Intron 8 of 10	5		ENSP00000462096.1
CNDP1	ENST00000582461.1	n.2048+519T>C		intron_variant	Intron 1 of 2	5
CNDP1	ENST00000584004.5	n.691+519T>C		intron_variant	Intron 4 of 6	2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34310 AN: 152006 Hom.: 3923 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.226

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.226 AC: 34356 AN: 152124 Hom.: 3937 Cov.: 31 AF XY: 0.228 AC XY: 16924 AN XY: 74354

African (AFR) AF: 0.256 AC: 10632 AN: 41512

American (AMR) AF: 0.264 AC: 4029 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 851 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1239 AN: 5162

South Asian (SAS) AF: 0.246 AC: 1188 AN: 4822

European-Finnish (FIN) AF: 0.221 AC: 2339 AN: 10580

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13316 AN: 67976

Other (OTH) AF: 0.229 AC: 482 AN: 2108

Alfa AF: 0.208 Hom.: 5675

Bravo AF: 0.230

Asia WGS AF: 0.251 AC: 872 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.5
DANN	Benign	0.81
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7229005; hg19: chr18-72246081; COSMIC: COSV107443104; COSMIC: COSV107443104;