rs374177752

Variant names:

• chr1-7665115-G-A
• rs374177752
• NM_015215.4:c.2568G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-7665115-G-A
• chr1-7665115-G-C
• chr1-7665115-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_015215.4(CAMTA1):​c.2568G>A​(p.Ser856Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,526,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: CAMTA1 NM_015215.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -2.16
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-7665115-G-A is Benign according to our data. Variant chr1-7665115-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210560.
• BP7: Synonymous conserved (PhyloP=-2.16 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000125 (19/152104) while in subpopulation NFE AF = 0.00025 (17/67992). AF 95% confidence interval is 0.000159. There are 0 homozygotes in GnomAd4. There are 10 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 19 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.2568G>A	p.Ser856Ser	synonymous	Exon 9 of 23	NP_056030.1	Q9Y6Y1-1
	CAMTA1	NM_001349608.2		c.2478G>A	p.Ser826Ser	synonymous	Exon 8 of 22	NP_001336537.1
	CAMTA1	NM_001349609.2		c.2568G>A	p.Ser856Ser	synonymous	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.2568G>A	p.Ser856Ser	synonymous	Exon 9 of 23	ENSP00000306522.6	Q9Y6Y1-1
	CAMTA1	ENST00000476864.2	TSL:1	c.2568G>A	p.Ser856Ser	synonymous	Exon 9 of 22	ENSP00000452319.2	A0A0C4DGL0
	CAMTA1	ENST00000700415.1		c.2478G>A	p.Ser826Ser	synonymous	Exon 8 of 23	ENSP00000514979.1	A0A8V8TQ65

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000153 AC: 26 AN: 170208 AF XY: 0.000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000209

Gnomad NFE exome AF: 0.000265

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000174 AC: 239 AN: 1374016 Hom.: 0 Cov.: 36 AF XY: 0.000176 AC XY: 119 AN XY: 674778

African (AFR) AF: 0.0000651 AC: 2 AN: 30712

American (AMR) AF: 0.00 AC: 0 AN: 32054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20418

East Asian (EAS) AF: 0.00 AC: 0 AN: 38996

South Asian (SAS) AF: 0.0000416 AC: 3 AN: 72128

European-Finnish (FIN) AF: 0.000132 AC: 6 AN: 45546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5350

European-Non Finnish (NFE) AF: 0.000208 AC: 223 AN: 1072122

Other (OTH) AF: 0.0000882 AC: 5 AN: 56690

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152104 Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10 AN XY: 74290

African (AFR) AF: 0.0000241 AC: 1 AN: 41430

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000734 Hom.: 0

Bravo AF: 0.0000907

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	0.45
DANN	Benign	0.85
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: rs374177752; hg19: chr1-7725175; COSMIC: COSV57931460;