dbSNP rs11079028: CNP:c.*191G>A (chr17-41974115-G-A) – 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.*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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.605

Publications

18 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=-0.84).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CNP	NM_033133.5 link	c.*191G>A	3_prime_UTR_variant	Exon 4 of 4	ENST00000393892.8	NP_149124.3	P09543-1
CNP	NM_001330216.2 link	c.*191G>A	3_prime_UTR_variant	Exon 4 of 4		NP_001317145.1	P09543-2A0A024R1T5
CNP	XM_011524340.3 link	c.*191G>A	3_prime_UTR_variant	Exon 4 of 4		XP_011522642.1	P09543-2A0A024R1T5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNP	ENST00000393892.8 link	c.*191G>A	3_prime_UTR_variant	Exon 4 of 4	1	NM_033133.5	ENSP00000377470.2	P09543-1
CNP	ENST00000393888.1 link	c.*191G>A	3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000377466.1	P09543-2
CNP	ENST00000472031.1 link	c.*634G>A	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000467641.1	K7EQ27
CNP	ENST00000486438.1 link	n.*153G>A	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

28811

AN:

149548

Hom.:

3581

Cov.:

show subpopulations

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.:

AF XY:

0.221

AC XY:

34859

AN XY:

157906

show subpopulations

African (AFR)

AF:

0.0529

AC:

443

AN:

8378

American (AMR)

AF:

0.346

AC:

3122

AN:

9012

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

1759

AN:

9784

East Asian (EAS)

AF:

0.429

AC:

9458

AN:

22044

South Asian (SAS)

AF:

0.210

AC:

2445

AN:

11634

European-Finnish (FIN)

AF:

0.231

AC:

4553

AN:

19710

Middle Eastern (MID)

AF:

0.178

AC:

254

AN:

1430

European-Non Finnish (NFE)

AF:

0.203

AC:

43087

AN:

211744

Other (OTH)

AF:

0.208

AC:

3782

AN:

18198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2427

4855

7282

9710

12137

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.193

AC:

28830

AN:

149658

Hom.:

3589

Cov.:

AF XY:

0.199

AC XY:

14525

AN XY:

72886

show subpopulations

African (AFR)

AF:

0.0547

AC:

2209

AN:

40350

American (AMR)

AF:

0.348

AC:

5200

AN:

14950

Ashkenazi Jewish (ASJ)

AF:

0.183

AC:

632

AN:

3456

East Asian (EAS)

AF:

0.398

AC:

2017

AN:

5066

South Asian (SAS)

AF:

0.251

AC:

1193

AN:

4750

European-Finnish (FIN)

AF:

0.250

AC:

2524

AN:

10088

Middle Eastern (MID)

AF:

0.188

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.214

AC:

14481

AN:

67738

Other (OTH)

AF:

0.199

AC:

411

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1065

2130

3196

4261

5326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.202

Hom.:

3750

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

(source)

DANN

Benign

0.43

PhyloP100

0.60

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

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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rs11079028

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