Genetic Variant NM_003418.5:c.-15+20C>A (chr3-129183756-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003418.5(CNBP):c.-15+20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,858 control chromosomes in the GnomAD database, including 17,690 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 0.45 ( 17580 hom., cov: 34)

Exomes 𝑓: 0.54 ( 110 hom. )

Consequence

CNBP
NM_003418.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

Publications

10 publications found

Variant links:

Genes affected

CNBP (HGNC:13164): (CCHC-type zinc finger nucleic acid binding protein) This gene encodes a nucleic-acid binding protein with seven zinc-finger domains. The protein has a preference for binding single stranded DNA and RNA. The protein functions in cap-independent translation of ornithine decarboxylase mRNA, and may also function in sterol-mediated transcriptional regulation. A CCTG expansion from <30 repeats to 75-11000 repeats in the first intron of this gene results in myotonic dystrophy type 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2016]

CNBP Gene-Disease associations (from GenCC):

myotonic dystrophy type 2
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

CNBP links:

ENSG00000289469 (HGNC:):

ENSG00000289469 links:

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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=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003418.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CNBP	NM_003418.5	MANE Select	c.-15+20C>A	intron	N/A	NP_003409.1
CNBP	NM_001127192.2		c.-15+20C>A	intron	N/A	NP_001120664.1
CNBP	NM_001127193.2		c.-15+20C>A	intron	N/A	NP_001120665.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CNBP	ENST00000422453.7	TSL:1 MANE Select	c.-15+20C>A	intron	N/A	ENSP00000410619.3
CNBP	ENST00000441626.6	TSL:2	c.-15+20C>A	intron	N/A	ENSP00000410769.2
CNBP	ENST00000451728.6	TSL:1	c.-15+20C>A	intron	N/A	ENSP00000399488.2

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68703

AN:

152058

Hom.:

17574

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.562

Gnomad AMR

AF:

0.544

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.588

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.485

GnomAD4 exome

AF:

0.541

AC:

370

AN:

684

Hom.:

110

Cov.:

AF XY:

0.578

AC XY:

266

AN XY:

460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.583

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.543

AC:

238

AN:

438

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.547

AC:

105

AN:

192

Other (OTH)

AF:

0.583

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.452

AC:

68711

AN:

152174

Hom.:

17580

Cov.:

AF XY:

0.457

AC XY:

33973

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.185

AC:

7705

AN:

41554

American (AMR)

AF:

0.545

AC:

8328

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.556

AC:

1932

AN:

3472

East Asian (EAS)

AF:

0.588

AC:

3036

AN:

5160

South Asian (SAS)

AF:

0.534

AC:

2581

AN:

4830

European-Finnish (FIN)

AF:

0.537

AC:

5693

AN:

10594

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.556

AC:

37781

AN:

67952

Other (OTH)

AF:

0.484

AC:

1024

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1777

3554

5331

7108

8885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.487

Hom.:

2346

Bravo

AF:

0.440

Asia WGS

AF:

0.520

AC:

1809

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.65

(source)

DANN

Benign

0.80

PhyloP100

-2.8

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over