17-4980523-C-G

Variant names:

• chr17-4980523-C-G
• rs238234
• NM_015099.4:c.799G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015099.4(CAMTA2):​c.799G>C​(p.Ala267Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,600,024 control chromosomes in the GnomAD database, including 502,365 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A267S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.82 (48756 hom., cov: 19)
  • Exomes 𝑓: 0.78 (453609 hom.)
• Consequence: CAMTA2 NM_015099.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.379
• Publications: 43 publications found

Genes affected

CAMTA2 (HGNC:18807): (calmodulin binding transcription activator 2) The protein encoded by this gene is a member of the calmodulin-binding transcription activator protein family. Members of this family share a common domain structure that consists of a transcription activation domain, a DNA-binding domain, and a calmodulin-binding domain. The encoded protein may be a transcriptional coactivator of genes involved in cardiac growth. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2010]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.3856694E-7).
• BP6: Variant 17-4980523-C-G is Benign according to our data. Variant chr17-4980523-C-G is described in ClinVar as Benign. ClinVar VariationId is 1270598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015099.4. 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
	CAMTA2	NM_015099.4	MANE Select	c.799G>C	p.Ala267Pro	missense	Exon 9 of 23	NP_055914.2
	CAMTA2	NM_001171167.2		c.868G>C	p.Ala290Pro	missense	Exon 9 of 23	NP_001164638.1	O94983-6
	CAMTA2	NM_001171168.2		c.796G>C	p.Ala266Pro	missense	Exon 8 of 22	NP_001164639.1	O94983-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA2	ENST00000348066.8	TSL:1 MANE Select	c.799G>C	p.Ala267Pro	missense	Exon 9 of 23	ENSP00000321813.7	O94983-1
	CAMTA2	ENST00000414043.7	TSL:1	c.868G>C	p.Ala290Pro	missense	Exon 9 of 23	ENSP00000412886.3	O94983-6
	CAMTA2	ENST00000361571.9	TSL:1	c.796G>C	p.Ala266Pro	missense	Exon 8 of 22	ENSP00000354828.5	O94983-4

Frequencies

GnomAD3 genomes AF: 0.816 AC: 117544 AN: 144116 Hom.: 48688 Cov.: 19

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.740

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.811

Gnomad OTH AF: 0.829

GnomAD2 exomes AF: 0.748 AC: 185915 AN: 248402 AF XY: 0.737

Gnomad AFR exome AF: 0.938

Gnomad AMR exome AF: 0.810

Gnomad ASJ exome AF: 0.743

Gnomad EAS exome AF: 0.493

Gnomad FIN exome AF: 0.712

Gnomad NFE exome AF: 0.815

Gnomad OTH exome AF: 0.779

GnomAD4 exome AF: 0.784 AC: 1141339 AN: 1455794 Hom.: 453609 Cov.: 35 AF XY: 0.776 AC XY: 562149 AN XY: 724316

African (AFR) AF: 0.939 AC: 31370 AN: 33410

American (AMR) AF: 0.811 AC: 36212 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 19512 AN: 26062

East Asian (EAS) AF: 0.496 AC: 19482 AN: 39298

South Asian (SAS) AF: 0.525 AC: 44946 AN: 85608

European-Finnish (FIN) AF: 0.724 AC: 38606 AN: 53290

Middle Eastern (MID) AF: 0.822 AC: 4730 AN: 5752

European-Non Finnish (NFE) AF: 0.813 AC: 899930 AN: 1107556

Other (OTH) AF: 0.773 AC: 46551 AN: 60194

GnomAD4 genome AF: 0.816 AC: 117677 AN: 144230 Hom.: 48756 Cov.: 19 AF XY: 0.806 AC XY: 56216 AN XY: 69740

African (AFR) AF: 0.933 AC: 35689 AN: 38260

American (AMR) AF: 0.831 AC: 11888 AN: 14300

Ashkenazi Jewish (ASJ) AF: 0.740 AC: 2523 AN: 3410

East Asian (EAS) AF: 0.483 AC: 2285 AN: 4728

South Asian (SAS) AF: 0.505 AC: 2250 AN: 4452

European-Finnish (FIN) AF: 0.699 AC: 6589 AN: 9432

Middle Eastern (MID) AF: 0.852 AC: 247 AN: 290

European-Non Finnish (NFE) AF: 0.811 AC: 53881 AN: 66466

Other (OTH) AF: 0.828 AC: 1655 AN: 2000

Alfa AF: 0.794 Hom.: 32898

Bravo AF: 0.835

TwinsUK AF: 0.799 AC: 2963

ALSPAC AF: 0.806 AC: 3107

ESP6500AA AF: 0.937 AC: 3851

ESP6500EA AF: 0.807 AC: 6766

ExAC AF: 0.751 AC: 90790

EpiCase AF: 0.807

EpiControl AF: 0.817

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.43
DANN	Benign	0.51
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.038	T
MetaRNN	Benign	7.4e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.38
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.044
Sift	Benign	1.0	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.026
MPC		0.28
ClinPred		0.0015	T
GERP RS		-2.1
Varity_R		0.035
gMVP		0.30
Mutation Taster		=76/24	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: rs238234; hg19: chr17-4883818; COSMIC: COSV61834037; COSMIC: COSV61834037;