rs4263028

Positions:

• chr18-74560889-G-A
• chr18-74560889-G-C

Variant summary

Our verdict is Benign. Variant got -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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP1	NM_032649.6	c.337G>A	p.Val113Ile	missense_variant	4/12	ENST00000358821.8	NP_116038.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP1	ENST00000358821.8	c.337G>A	p.Val113Ile	missense_variant	4/12	1	NM_032649.6	ENSP00000351682	P1
CNDP1	ENST00000582365.1	c.208G>A	p.Val70Ile	missense_variant	3/11	5		ENSP00000462096
CNDP1	ENST00000585136.1	n.469-1158G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.0602

Gnomad4 AMR exome AF: 0.00351

Gnomad4 ASJ exome AF: 0.000995

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000138

Gnomad4 OTH exome AF: 0.00333

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

Gnomad4 AFR AF: 0.0569

Gnomad4 AMR AF: 0.00432

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00503 Hom.: 12

Bravo AF: 0.0180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
Sift4G	Benign	0.59	T;T
Vest4		0.085
gMVP		0.11

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4263028; hg19: chr18-72228124;