Variant chr17-41968442-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033133.5(CNP):c.378C>T(p.His126=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,614,160 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 4 hom. )

Consequence

CNP
NM_033133.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.10

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 17-41968442-C-T is Benign according to our data. Variant chr17-41968442-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2647778.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0012 (182/152274) while in subpopulation NFE AF= 0.0021 (143/68034). AF 95% confidence interval is 0.00182. There are 1 homozygotes in gnomad4. There are 86 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CNP	NM_033133.5 linkuse as main transcript	c.378C>T	p.His126=	synonymous_variant	2/4	ENST00000393892.8
CNP	NM_001330216.2 linkuse as main transcript	c.318C>T	p.His106=	synonymous_variant	2/4
CNP	XM_011524340.3 linkuse as main transcript	c.318C>T	p.His106=	synonymous_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNP	ENST00000393892.8 linkuse as main transcript	c.378C>T	p.His126=	synonymous_variant	2/4	1	NM_033133.5	P3	P09543-1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

182

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00210

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000974

AC:

243

AN:

249496

Hom.:

AF XY:

0.00106

AC XY:

144

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000724

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.000835

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00118

AC:

1721

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

920

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000760

Gnomad4 ASJ exome

AF:

0.00119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00121

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00120

AC:

182

AN:

152274

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00210

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.000956

EpiCase

AF:

0.00153

EpiControl

AF:

0.00101

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

CNP: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.4

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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