Genetic Variant CNP:c.*1595T>C (chr17-41975519-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.13

Publications

22 publications found

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 Gene-Disease associations (from GenCC):

leukodystrophy, hypomyelinating, 20
Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

CNP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CNP	NM_033133.5 link	c.*1595T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000393892.8	NP_149124.3	P09543-1
CNP	NM_001330216.2 link	c.*1595T>C	3_prime_UTR_variant	Exon 4 of 4		NP_001317145.1	P09543-2A0A024R1T5
CNP	XM_011524340.3 link	c.*1595T>C	3_prime_UTR_variant	Exon 4 of 4		XP_011522642.1	P09543-2A0A024R1T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNP	ENST00000393892.8 link	c.*1595T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_033133.5	ENSP00000377470.2		P09543-1

Frequencies

GnomAD3 genomes

AF:

0.796

AC:

121032

AN:

151992

Hom.:

48850

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.881

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.865

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.929

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.796

AC:

121076

AN:

152110

Hom.:

48859

Cov.:

AF XY:

0.796

AC XY:

59164

AN XY:

74360

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1228

2456

3683

4911

6139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.51

(source)

DANN

Benign

0.78

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over