rs4796751

Variant names:

• chr17-41975519-T-C
• rs4796751
• NM_033133.5:c.*1595T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNP	NM_033133.5	MANE Select	c.*1595T>C		3_prime_UTR	Exon 4 of 4	NP_149124.3
	CNP	NM_001330216.2		c.*1595T>C		3_prime_UTR	Exon 4 of 4	NP_001317145.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNP	ENST00000393892.8	TSL:1 MANE Select	c.*1595T>C		3_prime_UTR	Exon 4 of 4	ENSP00000377470.2

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

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.865 AC: 64 AN: 74

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.929 AC: 39 AN: 42

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.651 AC: 27008 AN: 41462

American (AMR) AF: 0.872 AC: 13335 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3024 AN: 3472

East Asian (EAS) AF: 0.862 AC: 4452 AN: 5164

South Asian (SAS) AF: 0.854 AC: 4122 AN: 4828

European-Finnish (FIN) AF: 0.795 AC: 8425 AN: 10596

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.853 AC: 57984 AN: 67990

Other (OTH) AF: 0.808 AC: 1706 AN: 2112

Alfa AF: 0.837 Hom.: 193303

Bravo AF: 0.797

Asia WGS AF: 0.838 AC: 2913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.51
DANN	Benign	0.78
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4796751; hg19: chr17-40127537;