18-74571495-T-G

Variant names:

• chr18-74571495-T-G
• rs12964454
• NM_032649.6:c.841+225T>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.841+225T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,004 control chromosomes in the GnomAD database, including 9,541 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 0.33 (9541 hom., cov: 31)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 10 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 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.841+225T>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.841+225T>G		intron	N/A	ENSP00000351682.3	Q96KN2
	CNDP1	ENST00000864762.1		c.841+225T>G		intron	N/A	ENSP00000534821.1
	CNDP1	ENST00000954332.1		c.841+225T>G		intron	N/A	ENSP00000624391.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50205 AN: 151886 Hom.: 9537 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.330 AC: 50218 AN: 152004 Hom.: 9541 Cov.: 31 AF XY: 0.334 AC XY: 24807 AN XY: 74320

African (AFR) AF: 0.131 AC: 5442 AN: 41502

American (AMR) AF: 0.458 AC: 6984 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1170 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2411 AN: 5144

South Asian (SAS) AF: 0.351 AC: 1687 AN: 4812

European-Finnish (FIN) AF: 0.400 AC: 4225 AN: 10556

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26951 AN: 67954

Other (OTH) AF: 0.356 AC: 751 AN: 2108

Alfa AF: 0.380 Hom.: 21392

Bravo AF: 0.330

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.75
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12964454; hg19: chr18-72238730;