1-7232640-T-C

Variant names:

• chr1-7232640-T-C
• rs4908449
• NM_015215.4:c.303-16851T>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.303-16851T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,038 control chromosomes in the GnomAD database, including 37,306 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 0.69 (37306 hom., cov: 32)
• Consequence: CAMTA1 NM_015215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• 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), G2P, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMTA1	NM_015215.4	c.303-16851T>C		intron_variant	Intron 4 of 22	ENST00000303635.12	NP_056030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMTA1	ENST00000303635.12	c.303-16851T>C		intron_variant	Intron 4 of 22	1	NM_015215.4	ENSP00000306522.6

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104818 AN: 151922 Hom.: 37245 Cov.: 32

Gnomad AFR AF: 0.868

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.618

Gnomad OTH AF: 0.641

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

GnomAD4 genome AF: 0.690 AC: 104941 AN: 152038 Hom.: 37306 Cov.: 32 AF XY: 0.688 AC XY: 51114 AN XY: 74312

African (AFR) AF: 0.869 AC: 36050 AN: 41506

American (AMR) AF: 0.634 AC: 9681 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1907 AN: 3470

East Asian (EAS) AF: 0.727 AC: 3737 AN: 5140

South Asian (SAS) AF: 0.696 AC: 3348 AN: 4808

European-Finnish (FIN) AF: 0.580 AC: 6134 AN: 10572

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.618 AC: 41990 AN: 67950

Other (OTH) AF: 0.645 AC: 1360 AN: 2108

Alfa AF: 0.633 Hom.: 38068

Bravo AF: 0.699

Asia WGS AF: 0.750 AC: 2611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0010
DANN	Benign	0.31
PhyloP100		-2.6
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: rs4908449; hg19: chr1-7292700; COSMIC: COSV57888958;