chr18-74513504-G-A

Variant names:

• chr18-74513504-G-A
• rs2241510
• NM_018235.3:c.743-55G>A

Variant summary

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

The NM_018235.3(CNDP2):​c.743-55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,538,570 control chromosomes in the GnomAD database, including 31,836 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 0.18 (2851 hom., cov: 34)
  • Exomes 𝑓: 0.20 (28985 hom.)
• Consequence: CNDP2 NM_018235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.490
• Publications: 14 publications found

Genes affected

CNDP2 (HGNC:24437): (carnosine dipeptidase 2) CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18), is a nonspecific dipeptidase rather than a selective carnosinase (Teufel et al., 2003 [PubMed 12473676]).[supplied by OMIM, Mar 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNDP2	NM_018235.3	c.743-55G>A		intron_variant	Intron 7 of 11	ENST00000324262.9	NP_060705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262.9	c.743-55G>A		intron_variant	Intron 7 of 11	1	NM_018235.3	ENSP00000325548.4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28128 AN: 152166 Hom.: 2842 Cov.: 34

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.200 AC: 277426 AN: 1386286 Hom.: 28985 AF XY: 0.201 AC XY: 137291 AN XY: 683718

African (AFR) AF: 0.136 AC: 4367 AN: 32156

American (AMR) AF: 0.331 AC: 12501 AN: 37790

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 3317 AN: 22428

East Asian (EAS) AF: 0.309 AC: 11725 AN: 37894

South Asian (SAS) AF: 0.233 AC: 17662 AN: 75872

European-Finnish (FIN) AF: 0.120 AC: 4891 AN: 40760

Middle Eastern (MID) AF: 0.188 AC: 990 AN: 5258

European-Non Finnish (NFE) AF: 0.196 AC: 211119 AN: 1076440

Other (OTH) AF: 0.188 AC: 10854 AN: 57688

GnomAD4 genome AF: 0.185 AC: 28138 AN: 152284 Hom.: 2851 Cov.: 34 AF XY: 0.186 AC XY: 13854 AN XY: 74470

African (AFR) AF: 0.138 AC: 5737 AN: 41570

American (AMR) AF: 0.284 AC: 4338 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3472

East Asian (EAS) AF: 0.302 AC: 1560 AN: 5160

South Asian (SAS) AF: 0.237 AC: 1143 AN: 4832

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10622

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13012 AN: 68014

Other (OTH) AF: 0.190 AC: 401 AN: 2108

Alfa AF: 0.0695 Hom.: 92

Bravo AF: 0.194

Asia WGS AF: 0.275 AC: 957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.9
DANN	Benign	0.66
PhyloP100		0.49
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: rs2241510; hg19: chr18-72180739; COSMIC: COSV60840330; COSMIC: COSV60840330;