chr18-74584144-G-A

Variant names:

• chr18-74584144-G-A
• rs12957330
• NM_032649.6:c.1458-352G>A

Variant summary

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

The NM_032649.6(CNDP1):​c.1458-352G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 325,068 control chromosomes in the GnomAD database, including 4,387 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 0.13 (1717 hom., cov: 33)
  • Exomes 𝑓: 0.16 (2670 hom.)
• Consequence: CNDP1 NM_032649.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.918
• 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]

ZNF407-AS1 (HGNC:44331): (ZNF407 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	NM_032649.6	MANE Select	c.1458-352G>A		intron	N/A	NP_116038.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	ENST00000358821.8	TSL:1 MANE Select	c.1458-352G>A		intron	N/A	ENSP00000351682.3
	CNDP1	ENST00000582461.1	TSL:5	n.2774G>A		non_coding_transcript_exon	Exon 3 of 3
	CNDP1	ENST00000582365.1	TSL:5	c.1329-352G>A		intron	N/A	ENSP00000462096.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20407 AN: 152074 Hom.: 1719 Cov.: 33

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.0801

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.164 AC: 28308 AN: 172876 Hom.: 2670 Cov.: 0 AF XY: 0.162 AC XY: 14728 AN XY: 90806

African (AFR) AF: 0.0302 AC: 186 AN: 6158

American (AMR) AF: 0.133 AC: 985 AN: 7396

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 1173 AN: 5078

East Asian (EAS) AF: 0.0682 AC: 687 AN: 10068

South Asian (SAS) AF: 0.152 AC: 3081 AN: 20260

European-Finnish (FIN) AF: 0.156 AC: 1212 AN: 7746

Middle Eastern (MID) AF: 0.120 AC: 82 AN: 682

European-Non Finnish (NFE) AF: 0.183 AC: 19310 AN: 105680

Other (OTH) AF: 0.162 AC: 1592 AN: 9808

GnomAD4 genome AF: 0.134 AC: 20403 AN: 152192 Hom.: 1717 Cov.: 33 AF XY: 0.133 AC XY: 9923 AN XY: 74410

African (AFR) AF: 0.0339 AC: 1409 AN: 41522

American (AMR) AF: 0.127 AC: 1944 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3466

East Asian (EAS) AF: 0.0799 AC: 414 AN: 5184

South Asian (SAS) AF: 0.163 AC: 787 AN: 4820

European-Finnish (FIN) AF: 0.174 AC: 1845 AN: 10588

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.187 AC: 12711 AN: 68000

Other (OTH) AF: 0.128 AC: 270 AN: 2114

Alfa AF: 0.175 Hom.: 3963

Bravo AF: 0.127

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.5
DANN	Benign	0.72
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs12957330; hg19: chr18-72251380;