1-7767843-CAAA-CAA

Variant names:

• chr1-7767843-CA-C
• rs34335657
• ENST00000490905.5:c.*1334delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000490905.5(CAMTA1):​c.*1334delA variant causes a splice region change. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0082 (0 hom.)
• Consequence: CAMTA1 ENST00000490905.5 splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00
• Publications: 4 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), Ambry Genetics, G2P, Orphanet

ACMG classification

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

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000338 (46/136134) while in subpopulation AFR AF = 0.000516 (19/36828). AF 95% confidence interval is 0.000337. There are 0 homozygotes in GnomAd4. There are 26 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 46 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490905.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA1	NM_015215.4	MANE Select	c.*1365delA		3_prime_UTR	Exon 23 of 23	NP_056030.1	Q9Y6Y1-1
	CAMTA1	NM_001349608.2		c.*1365delA		3_prime_UTR	Exon 22 of 22	NP_001336537.1
	CAMTA1	NM_001349609.2		c.*1334delA		3_prime_UTR	Exon 23 of 23	NP_001336538.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA1	ENST00000490905.5	TSL:1	c.*1334delA		splice_region	Exon 6 of 6	ENSP00000452024.1	H0YJR7
	CAMTA1	ENST00000303635.12	TSL:1 MANE Select	c.*1365delA		3_prime_UTR	Exon 23 of 23	ENSP00000306522.6	Q9Y6Y1-1
	CAMTA1	ENST00000476864.2	TSL:1	c.*1334delA		3_prime_UTR	Exon 22 of 22	ENSP00000452319.2	A0A0C4DGL0

Frequencies

GnomAD3 genomes AF: 0.000338 AC: 46 AN: 136116 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000147

Gnomad ASJ AF: 0.00180

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000466

Gnomad FIN AF: 0.000303

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00820 AC: 2 AN: 244 Hom.: 0 Cov.: 0 AF XY: 0.00658 AC XY: 1 AN XY: 152

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 20

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00901 AC: 2 AN: 222

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000338 AC: 46 AN: 136134 Hom.: 0 Cov.: 0 AF XY: 0.000398 AC XY: 26 AN XY: 65360

African (AFR) AF: 0.000516 AC: 19 AN: 36828

American (AMR) AF: 0.000147 AC: 2 AN: 13626

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 6 AN: 3330

East Asian (EAS) AF: 0.00 AC: 0 AN: 4804

South Asian (SAS) AF: 0.000469 AC: 2 AN: 4268

European-Finnish (FIN) AF: 0.000303 AC: 2 AN: 6600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 270

European-Non Finnish (NFE) AF: 0.000236 AC: 15 AN: 63652

Other (OTH) AF: 0.00 AC: 0 AN: 1912

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

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: rs34335657; hg19: chr1-7827903;