NM_001355024.4:c.1448T>C

Variant names:

• chr12-75282301-A-G
• rs199705076
• NM_001355024.4:c.1448T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001355024.4(CAPS2):​c.1448T>C​(p.Ile483Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,608,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: CAPS2 NM_001355024.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.454
• Publications: 0 publications found

Genes affected

CAPS2 (HGNC:16471): (calcyphosine 2) Calcyphosine-2 is a calcium-binding protein with 2 EF-hand motifs (Wang et al., 2002 [PubMed 11846421]).[supplied by OMIM, Mar 2008]

CAPS2-AS1 (HGNC:40769): (CAPS2 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021560222).
• BP6: Variant 12-75282301-A-G is Benign according to our data. Variant chr12-75282301-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2388683.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355024.4. 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
	CAPS2	NM_001355024.4	MANE Select	c.1448T>C	p.Ile483Thr	missense	Exon 16 of 17	NP_001341953.2	Q9BXY5-4
	CAPS2	NM_001355023.4		c.1466T>C	p.Ile489Thr	missense	Exon 17 of 18	NP_001341952.2
	CAPS2	NM_032606.5		c.1619T>C	p.Ile540Thr	missense	Exon 17 of 18	NP_115995.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAPS2	ENST00000699294.1	MANE Select	c.1448T>C	p.Ile483Thr	missense	Exon 16 of 17	ENSP00000514274.1	Q9BXY5-4
	CAPS2	ENST00000393284.8	TSL:1	c.1562T>C	p.Ile521Thr	missense	Exon 16 of 17	ENSP00000376963.4	Q9BXY5-5
	CAPS2	ENST00000409799.6	TSL:1	c.1352T>C	p.Ile451Thr	missense	Exon 15 of 16	ENSP00000386977.2	B9A061

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000259 AC: 65 AN: 251196 AF XY: 0.000302

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000335

Gnomad OTH exome AF: 0.000653

GnomAD4 exome AF: 0.000260 AC: 379 AN: 1456322 Hom.: 0 Cov.: 27 AF XY: 0.000292 AC XY: 212 AN XY: 724976

African (AFR) AF: 0.0000600 AC: 2 AN: 33356

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00138 AC: 36 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.000293 AC: 324 AN: 1107026

Other (OTH) AF: 0.000216 AC: 13 AN: 60212

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74378

African (AFR) AF: 0.000217 AC: 9 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000353 AC: 24 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000490 Hom.: 1

Bravo AF: 0.000144

ExAC AF: 0.000239 AC: 29

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.26
DANN	Benign	0.71
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.45
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.026
Sift	Benign	0.47	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.37		Gain of MoRF binding (P = 0.0766)
MVP		0.18
MPC		0.085
ClinPred		0.0081	T
GERP RS		-0.45
Varity_R		0.046
gMVP		0.21
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs199705076; hg19: chr12-75676081;