Genetic Variant NM_015215.4:c.45+9C>T (chr1-6785584-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_015215.4(CAMTA1):c.45+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 907,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CAMTA1
NM_015215.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.531

Publications

0 publications found

Variant links:

Genes affected

CAMTA1 (HGNC:18806): (calmodulin binding transcription activator 1) The protein encoded by this gene contains a CG1 DNA-binding domain, a transcription factor immunoglobulin domain, ankyrin repeats, and calmodulin-binding IQ motifs. The encoded protein is thought to be a transcription factor and may be a tumor suppressor. However, a translocation event is sometimes observed between this gene and the WWTR1 gene, with the resulting WWTR1-CAMTA1 oncoprotein leading to epithelioid hemangioendothelioma, a malignant vascular cancer. [provided by RefSeq, Mar 2017]

CAMTA1 Gene-Disease associations (from GenCC):

cerebellar dysfunction with variable cognitive and behavioral abnormalities
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet

CAMTA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 1-6785584-C-T is Benign according to our data. Variant chr1-6785584-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2175151.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMTA1	NM_015215.4 link	c.45+9C>T		intron_variant	Intron 1 of 22	ENST00000303635.12	NP_056030.1	Q9Y6Y1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMTA1	ENST00000303635.12 link	c.45+9C>T		intron_variant	Intron 1 of 22	1	NM_015215.4	ENSP00000306522.6		Q9Y6Y1-1

Frequencies

GnomAD3 genomes

AF:

0.00000708

AC:

AN:

141238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000155

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

43706

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000661

AC:

AN:

907050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

428960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17044

American (AMR)

AF:

0.00

AC:

AN:

7310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8766

East Asian (EAS)

AF:

0.00

AC:

AN:

4708

South Asian (SAS)

AF:

0.00

AC:

AN:

27412

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2100

European-Non Finnish (NFE)

AF:

0.00000758

AC:

AN:

791942

Other (OTH)

AF:

0.00

AC:

AN:

30036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000708

AC:

AN:

141238

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

68492

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

39024

American (AMR)

AF:

0.00

AC:

AN:

14270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3344

East Asian (EAS)

AF:

0.00

AC:

AN:

4734

South Asian (SAS)

AF:

0.00

AC:

AN:

4570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

64360

Other (OTH)

AF:

0.00

AC:

AN:

1940

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 15, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

-0.53

PromoterAI

0.0074

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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_015215.4:c.45+9C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over