18-74555980-A-G

Variant names:

• chr18-74555980-A-G
• rs733686
• NM_032649.6:c.25-358A>G

Variant summary

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

The NM_032649.6(CNDP1):​c.25-358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,608 control chromosomes in the GnomAD database, including 31,991 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 0.64 (31991 hom., cov: 32)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032649.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	NM_032649.6	MANE Select	c.25-358A>G		intron	N/A	NP_116038.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	ENST00000358821.8	TSL:1 MANE Select	c.25-358A>G		intron	N/A	ENSP00000351682.3	Q96KN2
	CNDP1	ENST00000864762.1		c.25-358A>G		intron	N/A	ENSP00000534821.1
	CNDP1	ENST00000954332.1		c.25-358A>G		intron	N/A	ENSP00000624391.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97140 AN: 151492 Hom.: 31982 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.641 AC: 97181 AN: 151608 Hom.: 31991 Cov.: 32 AF XY: 0.643 AC XY: 47652 AN XY: 74066

African (AFR) AF: 0.461 AC: 19042 AN: 41294

American (AMR) AF: 0.727 AC: 11101 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2140 AN: 3452

East Asian (EAS) AF: 0.752 AC: 3828 AN: 5090

South Asian (SAS) AF: 0.658 AC: 3157 AN: 4798

European-Finnish (FIN) AF: 0.708 AC: 7469 AN: 10544

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48042 AN: 67860

Other (OTH) AF: 0.675 AC: 1421 AN: 2106

Alfa AF: 0.686 Hom.: 52568

Bravo AF: 0.636

Asia WGS AF: 0.671 AC: 2328 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.16
DANN	Benign	0.52
PhyloP100		-0.91
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: rs733686; hg19: chr18-72223215;