rs8078650

Positions:

• chr17-41968753-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393892.8(CNP):​c.676+13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,597,050 control chromosomes in the GnomAD database, including 29,245 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 0.21 (3954 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25291 hom.)
• Consequence: CNP ENST00000393892.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNP	NM_033133.5	c.676+13T>G		intron_variant		ENST00000393892.8	NP_149124.3
CNP	NM_001330216.2	c.616+13T>G		intron_variant			NP_001317145.1
CNP	XM_011524340.3	c.616+13T>G		intron_variant			XP_011522642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNP	ENST00000393892.8	c.676+13T>G		intron_variant		1	NM_033133.5	ENSP00000377470	P3
CNP	ENST00000393888.1	c.616+13T>G		intron_variant		1		ENSP00000377466	A1
CNP	ENST00000472031.1	c.3+1866T>G		intron_variant		2		ENSP00000467641

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32463 AN: 151994 Hom.: 3933 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.189

GnomAD3 exomes AF: 0.176 AC: 41145 AN: 233798 Hom.: 4115 AF XY: 0.175 AC XY: 22309 AN XY: 127796

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.0775

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.170

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.182 AC: 263227 AN: 1444938 Hom.: 25291 Cov.: 32 AF XY: 0.181 AC XY: 129503 AN XY: 716996

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.0824

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.249

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.214 AC: 32527 AN: 152112 Hom.: 3954 Cov.: 32 AF XY: 0.213 AC XY: 15835 AN XY: 74350

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.195

Alfa AF: 0.182 Hom.: 1662

Bravo AF: 0.207

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.2
DANN	Benign	0.62
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs8078650; hg19: chr17-40120771; COSMIC: COSV66368059; COSMIC: COSV66368059;