rs4796751

chr17-41975519-T-C

Variant summary

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

The NM_033133.5(CNP):c.*1595T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,238 control chromosomes in the GnomAD database, including 48,908 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 0.80 (48859 hom., cov: 31)
  • Exomes 𝑓: 0.88 (49 hom.)
• Consequence: CNP NM_033133.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNP	NM_033133.5	c.*1595T>C		3_prime_UTR_variant	4/4	ENST00000393892.8
CNP	NM_001330216.2	c.*1595T>C		3_prime_UTR_variant	4/4
CNP	XM_011524340.3	c.*1595T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNP	ENST00000393892.8	c.*1595T>C		3_prime_UTR_variant	4/4	1	NM_033133.5	P3

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121032 AN: 151992 Hom.: 48850 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.810

GnomAD4 exome AF: 0.883 AC: 113 AN: 128 Hom.: 49 Cov.: 0 AF XY: 0.881 AC XY: 74 AN XY: 84

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.865

Gnomad4 NFE exome AF: 0.929

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.796 AC: 121076 AN: 152110 Hom.: 48859 Cov.: 31 AF XY: 0.796 AC XY: 59164 AN XY: 74360

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.862

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.853

Gnomad4 OTH AF: 0.808

Alfa AF: 0.844 Hom.: 80889

Bravo AF: 0.797

Asia WGS AF: 0.838 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.51
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4796751; hg19: chr17-40127537;