chr1-7671670-T-C

Variant names:

• chr1-7671670-T-C
• rs4908473
• NM_015215.4:c.2779+633T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015215.4(CAMTA1):​c.2779+633T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,178 control chromosomes in the GnomAD database, including 1,812 homozygotes. 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: 𝑓 0.14 (1812 hom., cov: 33)
• Consequence: CAMTA1 NM_015215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

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.2779+633T>C		intron	N/A	NP_056030.1	Q9Y6Y1-1
	CAMTA1	NM_001349608.2		c.2689+633T>C		intron	N/A	NP_001336537.1
	CAMTA1	NM_001349609.2		c.2779+633T>C		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.2779+633T>C		intron	N/A	ENSP00000306522.6	Q9Y6Y1-1
	CAMTA1	ENST00000476864.2	TSL:1	c.2779+633T>C		intron	N/A	ENSP00000452319.2	A0A0C4DGL0
	CAMTA1	ENST00000495233.6	TSL:1	n.78+604T>C		intron	N/A	ENSP00000451720.2	H0YJK7

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20520 AN: 152058 Hom.: 1795 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.0465

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0825

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20583 AN: 152178 Hom.: 1812 Cov.: 33 AF XY: 0.135 AC XY: 10078 AN XY: 74410

African (AFR) AF: 0.199 AC: 8275 AN: 41512

American (AMR) AF: 0.236 AC: 3610 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0465 AC: 161 AN: 3466

East Asian (EAS) AF: 0.259 AC: 1338 AN: 5166

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4826

European-Finnish (FIN) AF: 0.0880 AC: 933 AN: 10608

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0825 AC: 5611 AN: 67984

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.105 Hom.: 3597

Bravo AF: 0.154

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.73
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

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: rs4908473; hg19: chr1-7731730;