rs200318010

Variant names:

• chr1-7663346-TC-T
• rs200318010
• NM_015215.4:c.806-5delC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_015215.4(CAMTA1):​c.806-5delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 1,519,790 control chromosomes in the GnomAD database, including 110 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0092 (107 hom.)
• Consequence: CAMTA1 NM_015215.4 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.23
• 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), Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 1-7663346-TC-T is Benign according to our data. Variant chr1-7663346-TC-T is described in ClinVar as Benign. ClinVar VariationId is 235450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00698 (1063/152332) while in subpopulation SAS AF = 0.0238 (115/4828). AF 95% confidence interval is 0.0203. There are 3 homozygotes in GnomAd4. There are 535 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1063 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA1	NM_015215.4	MANE Select	c.806-5delC		splice_region intron	N/A	NP_056030.1	Q9Y6Y1-1
	CAMTA1	NM_001349608.2		c.716-5delC		splice_region intron	N/A	NP_001336537.1
	CAMTA1	NM_001349609.2		c.806-5delC		splice_region intron	N/A	NP_001336538.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA1	ENST00000303635.12	TSL:1 MANE Select	c.806-6delC		splice_region intron	N/A	ENSP00000306522.6	Q9Y6Y1-1
	CAMTA1	ENST00000476864.2	TSL:1	c.806-6delC		splice_region intron	N/A	ENSP00000452319.2	A0A0C4DGL0
	CAMTA1	ENST00000700415.1		c.716-6delC		splice_region intron	N/A	ENSP00000514979.1	A0A8V8TQ65

Frequencies

GnomAD3 genomes AF: 0.00699 AC: 1064 AN: 152214 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00713

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00854 AC: 1558 AN: 182490 AF XY: 0.00931

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00553

Gnomad ASJ exome AF: 0.00366

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00337

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.0102

GnomAD4 exome AF: 0.00917 AC: 12546 AN: 1367458 Hom.: 107 Cov.: 31 AF XY: 0.00974 AC XY: 6514 AN XY: 668838

African (AFR) AF: 0.00144 AC: 44 AN: 30590

American (AMR) AF: 0.00576 AC: 179 AN: 31078

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 99 AN: 20190

East Asian (EAS) AF: 0.0000775 AC: 3 AN: 38724

South Asian (SAS) AF: 0.0245 AC: 1746 AN: 71392

European-Finnish (FIN) AF: 0.00403 AC: 200 AN: 49588

Middle Eastern (MID) AF: 0.0232 AC: 123 AN: 5312

European-Non Finnish (NFE) AF: 0.00907 AC: 9653 AN: 1064358

Other (OTH) AF: 0.00887 AC: 499 AN: 56226

GnomAD4 genome AF: 0.00698 AC: 1063 AN: 152332 Hom.: 3 Cov.: 33 AF XY: 0.00718 AC XY: 535 AN XY: 74490

African (AFR) AF: 0.00120 AC: 50 AN: 41588

American (AMR) AF: 0.00712 AC: 109 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.0238 AC: 115 AN: 4828

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10628

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0103 AC: 700 AN: 68018

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.00864 Hom.: 5

Bravo AF: 0.00657

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=100/0	polymorphism

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: rs200318010; hg19: chr1-7723406;