rs144242373

Variant names:

• chr1-7664502-C-T
• rs144242373
• NM_015215.4:c.1955C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_015215.4(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. 13/22 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 NM_015215.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.08
• 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 -20 ACMG points.

• 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 200 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.1955C>T	p.Ser652Leu	missense	Exon 9 of 23	NP_056030.1	Q9Y6Y1-1
	CAMTA1	NM_001349608.2		c.1865C>T	p.Ser622Leu	missense	Exon 8 of 22	NP_001336537.1
	CAMTA1	NM_001349609.2		c.1955C>T	p.Ser652Leu	missense	Exon 9 of 23	NP_001336538.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA1	ENST00000303635.12	TSL:1 MANE Select	c.1955C>T	p.Ser652Leu	missense	Exon 9 of 23	ENSP00000306522.6	Q9Y6Y1-1
	CAMTA1	ENST00000476864.2	TSL:1	c.1955C>T	p.Ser652Leu	missense	Exon 9 of 22	ENSP00000452319.2	A0A0C4DGL0
	CAMTA1	ENST00000700415.1		c.1865C>T	p.Ser622Leu	missense	Exon 8 of 23	ENSP00000514979.1	A0A8V8TQ65

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 200 AN: 152236 Hom.: 1 Cov.: 33

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

GnomAD2 exomes AF: 0.00128 AC: 320 AN: 250170 AF XY: 0.00128

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 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.: 4 Cov.: 36 AF XY: 0.00162 AC XY: 1180 AN XY: 726796

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00136 AC: 61 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.0000762 AC: 4 AN: 52474

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00202 AC: 2243 AN: 1112010

Other (OTH) AF: 0.00147 AC: 89 AN: 60388

GnomAD4 genome AF: 0.00131 AC: 200 AN: 152354 Hom.: 1 Cov.: 33 AF XY: 0.00110 AC XY: 82 AN XY: 74500

African (AFR) AF: 0.000216 AC: 9 AN: 41596

American (AMR) AF: 0.00124 AC: 19 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00243 AC: 165 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00189 Hom.: 3

Bravo AF: 0.00132

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00140 AC: 12

ExAC AF: 0.00128 AC: 156

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00273

EpiControl AF: 0.00237

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Cerebellar dysfunction with variable cognitive and behavioral abnormalities (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.0078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.068
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.060	T
Polyphen		0.76	P
Vest4		0.47
MVP		0.15
MPC		0.70
ClinPred		0.033	T
GERP RS		5.1
Varity_R		0.13
gMVP		0.44
Mutation Taster		=92/8	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: rs144242373; hg19: chr1-7724562; COSMIC: COSV57893878;