Genetic Variant CNN3:c.385-75G>A (chr1-94901860-C-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_001839.5(CNN3):c.385-75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0941 in 1,064,266 control chromosomes in the GnomAD database, including 5,249 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 0.091 ( 701 hom., cov: 32)

Exomes 𝑓: 0.095 ( 4548 hom. )

Consequence

CNN3
NM_001839.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.871

Publications

8 publications found

Variant links:

Genes affected

CNN3 (HGNC:2157): (calponin 3) This gene encodes a protein with a markedly acidic C terminus; the basic N-terminus is highly homologous to the N-terminus of a related gene, CNN1. Members of the CNN gene family all contain similar tandemly repeated motifs. This encoded protein is associated with the cytoskeleton but is not involved in contraction. [provided by RefSeq, Jul 2008]

CNN3 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 (NFE) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001839.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CNN3	NM_001839.5	MANE Select	c.385-75G>A	intron	N/A	NP_001830.1
CNN3	NM_001286056.2		c.262-75G>A	intron	N/A	NP_001272985.1
CNN3	NM_001286055.2		c.247-75G>A	intron	N/A	NP_001272984.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CNN3	ENST00000370206.9	TSL:1 MANE Select	c.385-75G>A	intron	N/A	ENSP00000359225.4
CNN3	ENST00000885995.1		c.385-75G>A	intron	N/A	ENSP00000556054.1
CNN3	ENST00000939684.1		c.379-75G>A	intron	N/A	ENSP00000609743.1

Frequencies

GnomAD3 genomes

AF:

0.0907

AC:

13783

AN:

152022

Hom.:

701

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0688

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.0792

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.0506

Gnomad SAS

AF:

0.0518

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.0995

GnomAD4 exome

AF:

0.0947

AC:

86416

AN:

912126

Hom.:

4548

Cov.:

AF XY:

0.0939

AC XY:

44313

AN XY:

472054

show subpopulations

African (AFR)

AF:

0.0651

AC:

1408

AN:

21630

American (AMR)

AF:

0.0621

AC:

2099

AN:

33816

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

2572

AN:

20622

East Asian (EAS)

AF:

0.0515

AC:

1879

AN:

36460

South Asian (SAS)

AF:

0.0588

AC:

3996

AN:

67946

European-Finnish (FIN)

AF:

0.104

AC:

5138

AN:

49608

Middle Eastern (MID)

AF:

0.129

AC:

590

AN:

4588

European-Non Finnish (NFE)

AF:

0.102

AC:

64789

AN:

635542

Other (OTH)

AF:

0.0941

AC:

3945

AN:

41914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3927

7854

11780

15707

19634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1662

3324

4986

6648

8310

<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:

0.0906

AC:

13782

AN:

152140

Hom.:

701

Cov.:

AF XY:

0.0889

AC XY:

6609

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0687

AC:

2850

AN:

41512

American (AMR)

AF:

0.0791

AC:

1208

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.124

AC:

432

AN:

3470

East Asian (EAS)

AF:

0.0509

AC:

264

AN:

5190

South Asian (SAS)

AF:

0.0512

AC:

246

AN:

4800

European-Finnish (FIN)

AF:

0.100

AC:

1060

AN:

10584

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.107

AC:

7245

AN:

67992

Other (OTH)

AF:

0.0990

AC:

209

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

642

1284

1925

2567

3209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.104

Hom.:

1475

Bravo

AF:

0.0904

Asia WGS

AF:

0.0800

AC:

279

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.9

(source)

DANN

Benign

0.17

PhyloP100

-0.87

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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