chr18-74560889-G-A

Variant names:

• chr18-74560889-G-A
• rs4263028
• NM_032649.6:c.337G>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.337G>A​(p.Val113Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00314 in 1,614,022 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (69 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (59 hom.)
• Consequence: CNDP1 NM_032649.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 21 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 (MetaRNN=0.0046834648).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.055 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.337G>A	p.Val113Ile	missense	Exon 4 of 12	NP_116038.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP1	ENST00000358821.8	TSL:1 MANE Select	c.337G>A	p.Val113Ile	missense	Exon 4 of 12	ENSP00000351682.3
	CNDP1	ENST00000582365.1	TSL:5	c.208G>A	p.Val70Ile	missense	Exon 3 of 11	ENSP00000462096.1
	CNDP1	ENST00000585136.1	TSL:3	n.469-1158G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0162 AC: 2458 AN: 152080 Hom.: 70 Cov.: 31

Gnomad AFR AF: 0.0569

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00178 AC: 2595 AN: 1461824 Hom.: 59 Cov.: 31 AF XY: 0.00153 AC XY: 1111 AN XY: 727204

African (AFR) AF: 0.0602 AC: 2016 AN: 33478

American (AMR) AF: 0.00351 AC: 157 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000359 AC: 31 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5768

European-Non Finnish (NFE) AF: 0.000138 AC: 153 AN: 1111980

Other (OTH) AF: 0.00333 AC: 201 AN: 60394

GnomAD4 genome AF: 0.0162 AC: 2465 AN: 152198 Hom.: 69 Cov.: 31 AF XY: 0.0155 AC XY: 1156 AN XY: 74400

African (AFR) AF: 0.0569 AC: 2361 AN: 41508

American (AMR) AF: 0.00432 AC: 66 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68014

Other (OTH) AF: 0.0114 AC: 24 AN: 2106

Alfa AF: 0.0103 Hom.: 40

Bravo AF: 0.0180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.2
DEOGEN2	Benign	0.013	T
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0047	T
PhyloP100		0.22
Sift4G	Benign	0.59	T
Vest4		0.085
gMVP		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4263028; hg19: chr18-72228124;