rs2070106

Positions:

• chr17-41973846-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_033133.5(CNP):​c.1188G>A​(p.Gly396=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,603,894 control chromosomes in the GnomAD database, including 83,452 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 0.25 (5851 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77601 hom.)
• Consequence: CNP NM_033133.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

Genes affected

CNP (HGNC:2158): (2',3'-cyclic nucleotide 3' phosphodiesterase) Predicted to enable 2',3'-cyclic-nucleotide 3'-phosphodiesterase activity. Involved in substantia nigra development. Located in several cellular components, including extracellular space; microtubule; and plasma membrane. Implicated in hypomyelinating leukodystrophy 20; multiple sclerosis; and schizophrenia. Biomarker of alcoholic liver cirrhosis; multiple sclerosis; and restless legs syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNP	NM_033133.5	c.1188G>A	p.Gly396=	synonymous_variant	4/4	ENST00000393892.8
CNP	NM_001330216.2	c.1128G>A	p.Gly376=	synonymous_variant	4/4
CNP	XM_011524340.3	c.1128G>A	p.Gly376=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNP	ENST00000393892.8	c.1188G>A	p.Gly396=	synonymous_variant	4/4	1	NM_033133.5	P3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38717 AN: 151876 Hom.: 5853 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.277

GnomAD3 exomes AF: 0.305 AC: 73361 AN: 240248 Hom.: 12077 AF XY: 0.316 AC XY: 41221 AN XY: 130414

Gnomad AFR exome AF: 0.0955

Gnomad AMR exome AF: 0.222

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.416

Gnomad SAS exome AF: 0.392

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.319

GnomAD4 exome AF: 0.322 AC: 467805 AN: 1451900 Hom.: 77601 Cov.: 44 AF XY: 0.326 AC XY: 235241 AN XY: 721230

Gnomad4 AFR exome AF: 0.0933

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.405

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.327

Gnomad4 OTH exome AF: 0.317

GnomAD4 genome AF: 0.255 AC: 38726 AN: 151994 Hom.: 5851 Cov.: 32 AF XY: 0.254 AC XY: 18863 AN XY: 74262

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.280

Alfa AF: 0.307 Hom.: 9531

Bravo AF: 0.248

Asia WGS AF: 0.378 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: 34

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070106; hg19: chr17-40125864; COSMIC: COSV57268032; COSMIC: COSV57268032;