Genetic Variant NM_033133.5:c.*1118T>C (chr17-41975042-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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0970

Publications

7 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=-0.77).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CNP	NM_033133.5 link	c.*1118T>C	3_prime_UTR_variant	Exon 4 of 4	ENST00000393892.8	NP_149124.3	P09543-1
CNP	NM_001330216.2 link	c.*1118T>C	3_prime_UTR_variant	Exon 4 of 4		NP_001317145.1	P09543-2A0A024R1T5
CNP	XM_011524340.3 link	c.*1118T>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.*1118T>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_033133.5	ENSP00000377470.2		P09543-1
CNP	ENST00000393888.1 link	c.*1118T>C		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000377466.1		P09543-2

Frequencies

GnomAD3 genomes

AF:

0.0399

AC:

6070

AN:

152188

Hom.:

172

Cov.:

show subpopulations

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:

AN:

104

Hom.:

Cov.:

AF XY:

0.0500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0244

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0399

AC:

6070

AN:

152306

Hom.:

172

Cov.:

AF XY:

0.0382

AC XY:

2847

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0107

AC:

446

AN:

41564

American (AMR)

AF:

0.0529

AC:

809

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0706

AC:

245

AN:

3472

East Asian (EAS)

AF:

0.000578

AC:

AN:

5186

South Asian (SAS)

AF:

0.0116

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0386

AC:

410

AN:

10620

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0575

AC:

3913

AN:

68020

Other (OTH)

AF:

0.0535

AC:

113

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

298

595

893

1190

1488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0578

Hom.:

414

Bravo

AF:

0.0403

Asia WGS

AF:

0.00664

AC:

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

(source)

DANN

Benign

0.72

PhyloP100

-0.097

Mutation Taster

=100/0

polymorphism

(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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NM_033133.5:c.*1118T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over