17-41971920-G-C

Position:

chr17-41971920-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_033133.5(CNP):c.705G>C(p.Lys235Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,613,912 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

CNP
NM_033133.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.06

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005069673).

BP6

Variant 17-41971920-G-C is Benign according to our data. Variant chr17-41971920-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2647779.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000966 (147/152100) while in subpopulation NFE AF= 0.00166 (113/67986). AF 95% confidence interval is 0.00141. There are 1 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CNP	NM_033133.5 linkuse as main transcript	c.705G>C	p.Lys235Asn	missense_variant	3/4	ENST00000393892.8
CNP	NM_001330216.2 linkuse as main transcript	c.645G>C	p.Lys215Asn	missense_variant	3/4
CNP	XM_011524340.3 linkuse as main transcript	c.645G>C	p.Lys215Asn	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNP	ENST00000393892.8 linkuse as main transcript	c.705G>C	p.Lys235Asn	missense_variant	3/4	1	NM_033133.5	P3	P09543-1

Frequencies

GnomAD3 genomes

AF:

0.000967

AC:

147

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00126

AC:

312

AN:

248312

Hom.:

AF XY:

0.00109

AC XY:

147

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000417

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.00479

GnomAD4 exome

AF:

0.00122

AC:

1780

AN:

1461812

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

861

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.000966

AC:

147

AN:

152100

Hom.:

Cov.:

AF XY:

0.000794

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00144

Hom.:

Bravo

AF:

0.00121

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000250

AC:

ESP6500EA

AF:

0.000837

AC:

ExAC

AF:

0.00149

AC:

180

EpiCase

AF:

0.00131

EpiControl

AF:

0.00124

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CNP-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

CNP: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

0.85

D;D;D;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.027

D;D

Sift4G

Benign

0.070

T;T

Polyphen

0.99

D;.

Vest4

0.34

MutPred

0.50

Loss of ubiquitination at K235 (P = 0.0063);.;

MVP

0.76

MPC

0.67

ClinPred

0.044

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.42

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over