18-74561977-G-T

Variant names:

• chr18-74561977-G-T
• rs9967490
• NM_032649.6:c.467-70G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032649.6(CNDP1):​c.467-70G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44
• Publications: 12 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]

ENSG00000264340 (HGNC:58557):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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.467-70G>T		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.467-70G>T		intron	N/A	ENSP00000351682.3	Q96KN2
	CNDP1	ENST00000864762.1		c.467-70G>T		intron	N/A	ENSP00000534821.1
	CNDP1	ENST00000954332.1		c.467-70G>T		intron	N/A	ENSP00000624391.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1149920 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 585712

African (AFR) AF: 0.00 AC: 0 AN: 27370

American (AMR) AF: 0.00 AC: 0 AN: 43370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23908

East Asian (EAS) AF: 0.00 AC: 0 AN: 37924

South Asian (SAS) AF: 0.00 AC: 0 AN: 79048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5160

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 831400

Other (OTH) AF: 0.00 AC: 0 AN: 49840

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 12887

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0020
DANN	Benign	0.36
PhyloP100		-3.4

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: rs9967490; hg19: chr18-72229212;