Genetic Variant CNBP: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNBP	NM_003418.5 link	c.-15+20C>A		intron_variant	Intron 1 of 4	ENST00000422453.7	NP_003409.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CNBP	ENST00000422453.7 link	c.-15+20C>A	intron_variant	Intron 1 of 4	1	NM_003418.5	ENSP00000410619.3
CNBP	ENST00000441626.6 link	c.-15+20C>A	intron_variant	Intron 1 of 4	2		ENSP00000410769.2
CNBP	ENST00000451728.6 link	c.-15+20C>A	intron_variant	Intron 1 of 4	1		ENSP00000399488.2
CNBP	ENST00000446936.6 link	c.-15+20C>A	intron_variant	Intron 1 of 4	1		ENSP00000400444.2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over