Genetic Variant NM_015215.4:c.45+5G>C (chr1-6785580-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015215.4(CAMTA1):c.45+5G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CAMTA1
NM_015215.4 splice_region, intron

Scores

Splicing: ADA: 0.5398

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

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), Ambry Genetics, G2P, Orphanet

CAMTA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015215.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAMTA1	NM_015215.4	MANE Select	c.45+5G>C	splice_region intron	N/A	NP_056030.1	Q9Y6Y1-1
CAMTA1	NM_001349608.2		c.25+5G>C	splice_region intron	N/A	NP_001336537.1
CAMTA1	NM_001349609.2		c.45+5G>C	splice_region intron	N/A	NP_001336538.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAMTA1	ENST00000303635.12	TSL:1 MANE Select	c.45+5G>C	splice_region intron	N/A	ENSP00000306522.6	Q9Y6Y1-1
CAMTA1	ENST00000476864.2	TSL:1	c.45+5G>C	splice_region intron	N/A	ENSP00000452319.2	A0A0C4DGL0
CAMTA1	ENST00000473578.5	TSL:1	c.45+5G>C	splice_region intron	N/A	ENSP00000451388.1	Q9Y6Y1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

911184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

431382

African (AFR)

AF:

0.00

AC:

AN:

17104

American (AMR)

AF:

0.00

AC:

AN:

7498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9022

East Asian (EAS)

AF:

0.00

AC:

AN:

4818

South Asian (SAS)

AF:

0.00

AC:

AN:

27960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2152

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

794314

Other (OTH)

AF:

0.00

AC:

AN:

30240

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

1.2

PromoterAI

-0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.54

dbscSNV1_RF

Benign

0.57

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over