chr1-6785584-C-A

Variant names:

• chr1-6785584-C-A
• rs1262386246
• NM_015215.4:c.45+9C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015215.4(CAMTA1):​c.45+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000011 in 907,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 26)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: CAMTA1 NM_015215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 0 publications found

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

ACMG classification

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=-0.36).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000110 AC: 1 AN: 907050 Hom.: 0 Cov.: 31 AF XY: 0.00000233 AC XY: 1 AN XY: 428960

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

African (AFR) AF: 0.00 AC: 0 AN: 17044

American (AMR) AF: 0.00 AC: 0 AN: 7310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8766

East Asian (EAS) AF: 0.00 AC: 0 AN: 4708

South Asian (SAS) AF: 0.00 AC: 0 AN: 27412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17732

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2100

European-Non Finnish (NFE) AF: 0.00000126 AC: 1 AN: 791942

Other (OTH) AF: 0.00 AC: 0 AN: 30036

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.90
PhyloP100		-0.53
PromoterAI		0.029	Neutral
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

Other links and lift over

dbSNP: rs1262386246; hg19: chr1-6845644;