rs144242373

Positions:

chr1-7664502-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000303635.12(CAMTA1):c.1955C>T(p.Ser652Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00162 in 1,613,292 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S652W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 4 hom. )

Consequence

CAMTA1
ENST00000303635.12 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.08

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CAMTA1. . Gene score misZ 3.2619 (greater than the threshold 3.09). Trascript score misZ 4.755 (greater than threshold 3.09). GenCC has associacion of gene with cerebellar dysfunction with variable cognitive and behavioral abnormalities.

BP4

Computational evidence support a benign effect (MetaRNN=0.0078443885).

BP6

Variant 1-7664502-C-T is Benign according to our data. Variant chr1-7664502-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 377146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00131 (200/152354) while in subpopulation NFE AF= 0.00243 (165/68028). AF 95% confidence interval is 0.00212. There are 1 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 200 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMTA1	NM_015215.4 linkuse as main transcript	c.1955C>T	p.Ser652Leu	missense_variant	9/23	ENST00000303635.12	NP_056030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMTA1	ENST00000303635.12 linkuse as main transcript	c.1955C>T	p.Ser652Leu	missense_variant	9/23	1	NM_015215.4	ENSP00000306522	P2	Q9Y6Y1-1

Frequencies

GnomAD3 genomes

AF:

0.00131

AC:

200

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00243

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00128

AC:

320

AN:

250170

Hom.:

AF XY:

0.00128

AC XY:

173

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00148

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00223

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00165

AC:

2412

AN:

1460938

Hom.:

Cov.:

AF XY:

0.00162

AC XY:

1180

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000762

Gnomad4 NFE exome

AF:

0.00202

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00131

AC:

200

AN:

152354

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000216

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00243

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00198

Hom.:

Bravo

AF:

0.00132

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00128

AC:

156

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00273

EpiControl

AF:

0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	CAMTA1: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Nov 07, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -

Cerebellar dysfunction with variable cognitive and behavioral abnormalities

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0081

MetaRNN

Benign

0.0078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

MutationTaster

Benign

0.74

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.0

REVEL

Benign

0.068

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.060

Polyphen

0.76

Vest4

0.47

MVP

0.15

MPC

0.70

ClinPred

0.033

GERP RS

5.1

Varity_R

0.13

gMVP

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over