chr17-41975042-T-C

Position:

• chr17-41975042-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.*1118T>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 0.0399 in 152,410 control chromosomes in the GnomAD database, including 172 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 0.040 (172 hom., cov: 32)
  • Exomes 𝑓: 0.038 (0 hom.)
• Consequence: CNP NM_033133.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNP	NM_033133.5	c.*1118T>C		3_prime_UTR_variant	4/4	ENST00000393892.8
CNP	NM_001330216.2	c.*1118T>C		3_prime_UTR_variant	4/4
CNP	XM_011524340.3	c.*1118T>C		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNP	ENST00000393892.8	c.*1118T>C		3_prime_UTR_variant	4/4	1	NM_033133.5	P3
CNP	ENST00000393888.1	c.*1118T>C		3_prime_UTR_variant	4/4	1		A1

Frequencies

GnomAD3 genomes AF: 0.0399 AC: 6070 AN: 152188 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0575

Gnomad OTH AF: 0.0541

GnomAD4 exome AF: 0.0385 AC: 4 AN: 104 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 4 AN XY: 80

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.0244

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0399 AC: 6070 AN: 152306 Hom.: 172 Cov.: 32 AF XY: 0.0382 AC XY: 2847 AN XY: 74486

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0575

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0593 Hom.: 307

Bravo AF: 0.0403

Asia WGS AF: 0.00664 AC: 23 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	9.7
DANN	Benign	0.72

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: rs11296; hg19: chr17-40127060;