1-6825226-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015215.4(CAMTA1):c.234+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,433,486 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (11 hom.)
• Consequence: CAMTA1 NM_015215.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.265

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 1-6825226-T-C is Benign according to our data. Variant chr1-6825226-T-C is described in ClinVar as [Benign]. Clinvar id is 1987599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00774 (1178/152290) while in subpopulation AFR AF= 0.027 (1121/41546). AF 95% confidence interval is 0.0257. There are 14 homozygotes in gnomad4. There are 563 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1172 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMTA1	NM_015215.4	c.234+16T>C		intron_variant		ENST00000303635.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMTA1	ENST00000303635.12	c.234+16T>C		intron_variant		1	NM_015215.4	P2

Frequencies

GnomAD3 genomes AF: 0.00770 AC: 1172 AN: 152172 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00268

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00207 AC: 441 AN: 212836 Hom.: 4 AF XY: 0.00151 AC XY: 176 AN XY: 116502

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.00132

Gnomad ASJ exome AF: 0.000519

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000427

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000578

Gnomad OTH exome AF: 0.000613

GnomAD4 exome AF: 0.000705 AC: 903 AN: 1281196 Hom.: 11 Cov.: 17 AF XY: 0.000588 AC XY: 379 AN XY: 644888

Gnomad4 AFR exome AF: 0.0255

Gnomad4 AMR exome AF: 0.00137

Gnomad4 ASJ exome AF: 0.000389

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000529

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000257

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00774 AC: 1178 AN: 152290 Hom.: 14 Cov.: 32 AF XY: 0.00756 AC XY: 563 AN XY: 74464

Gnomad4 AFR AF: 0.0270

Gnomad4 AMR AF: 0.00268

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00488 Hom.: 1

Bravo AF: 0.00868

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	18
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs150579824; hg19: chr1-6885286;