rs11079028

Positions:

• chr17-41974115-G-A
• chr17-41974115-G-C
• chr17-41974115-G-T

Variant summary

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

The NM_033133.5(CNP):​c.*191G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 461,592 control chromosomes in the GnomAD database, including 12,267 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 0.19 (3589 hom., cov: 30)
  • Exomes 𝑓: 0.22 (8678 hom.)
• Consequence: CNP NM_033133.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNP	NM_033133.5	c.*191G>A		3_prime_UTR_variant	4/4	ENST00000393892.8
CNP	NM_001330216.2	c.*191G>A		3_prime_UTR_variant	4/4
CNP	XM_011524340.3	c.*191G>A		3_prime_UTR_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNP	ENST00000393892.8	c.*191G>A		3_prime_UTR_variant	4/4	1	NM_033133.5	P3
CNP	ENST00000393888.1	c.*191G>A		3_prime_UTR_variant	4/4	1		A1
CNP	ENST00000472031.1	c.*634G>A		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.193 AC: 28811 AN: 149548 Hom.: 3581 Cov.: 30

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.196

GnomAD4 exome AF: 0.221 AC: 68903 AN: 311934 Hom.: 8678 Cov.: 5 AF XY: 0.221 AC XY: 34859 AN XY: 157906

Gnomad4 AFR exome AF: 0.0529

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.193 AC: 28830 AN: 149658 Hom.: 3589 Cov.: 30 AF XY: 0.199 AC XY: 14525 AN XY: 72886

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.199

Alfa AF: 0.217 Hom.: 2757

Bravo AF: 0.192

Asia WGS AF: 0.300 AC: 1042 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.3
DANN	Benign	0.43
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.1

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: rs11079028; hg19: chr17-40126133; COSMIC: COSV57270841; COSMIC: COSV57270841;