rs2070106

Variant names:

• chr17-41973846-G-A
• rs2070106
• NM_033133.5:c.1188G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_033133.5(CNP):​c.1188G>A​(p.Gly396Gly) 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
• Publications: 43 publications found

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]

CNP Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 20

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033133.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNP	NM_033133.5	MANE Select	c.1188G>A	p.Gly396Gly	synonymous	Exon 4 of 4	NP_149124.3
	CNP	NM_001330216.2		c.1128G>A	p.Gly376Gly	synonymous	Exon 4 of 4	NP_001317145.1	P09543-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNP	ENST00000393892.8	TSL:1 MANE Select	c.1188G>A	p.Gly396Gly	synonymous	Exon 4 of 4	ENSP00000377470.2	P09543-1
	CNP	ENST00000393888.1	TSL:1	c.1128G>A	p.Gly376Gly	synonymous	Exon 4 of 4	ENSP00000377466.1	P09543-2
	CNP	ENST00000472031.1	TSL:2	c.*365G>A		3_prime_UTR	Exon 3 of 3	ENSP00000467641.1	K7EQ27

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

GnomAD2 exomes AF: 0.305 AC: 73361 AN: 240248 AF XY: 0.316

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 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

African (AFR) AF: 0.0933 AC: 3110 AN: 33324

American (AMR) AF: 0.224 AC: 9853 AN: 43896

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 10308 AN: 25468

East Asian (EAS) AF: 0.400 AC: 15837 AN: 39546

South Asian (SAS) AF: 0.392 AC: 33259 AN: 84872

European-Finnish (FIN) AF: 0.247 AC: 12965 AN: 52574

Middle Eastern (MID) AF: 0.344 AC: 1967 AN: 5714

European-Non Finnish (NFE) AF: 0.327 AC: 361522 AN: 1106588

Other (OTH) AF: 0.317 AC: 18984 AN: 59918

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

African (AFR) AF: 0.101 AC: 4205 AN: 41492

American (AMR) AF: 0.259 AC: 3954 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1420 AN: 3464

East Asian (EAS) AF: 0.396 AC: 2028 AN: 5126

South Asian (SAS) AF: 0.404 AC: 1947 AN: 4818

European-Finnish (FIN) AF: 0.230 AC: 2430 AN: 10556

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21801 AN: 67934

Other (OTH) AF: 0.280 AC: 591 AN: 2114

Alfa AF: 0.301 Hom.: 13043

Bravo AF: 0.248

Asia WGS AF: 0.378 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.84
PhyloP100		-2.3
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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