rs12318506

Variant names:

• chr12-75324643-G-T
• rs12318506
• NM_001355024.4:c.131+596C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001355024.4(CAPS2):​c.131+596C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.085 in 151,940 control chromosomes in the GnomAD database, including 767 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.085 (767 hom., cov: 32)
• Consequence: CAPS2 NM_001355024.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 5 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 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPS2	NM_001355024.4	c.131+596C>A		intron_variant	Intron 3 of 16	ENST00000699294.1	NP_001341953.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPS2	ENST00000699294.1	c.131+596C>A		intron_variant	Intron 3 of 16		NM_001355024.4	ENSP00000514274.1

Frequencies

GnomAD3 genomes AF: 0.0850 AC: 12901 AN: 151824 Hom.: 766 Cov.: 32

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0530

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.0466

Gnomad MID AF: 0.0764

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0729

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0850 AC: 12910 AN: 151940 Hom.: 767 Cov.: 32 AF XY: 0.0834 AC XY: 6194 AN XY: 74274

African (AFR) AF: 0.179 AC: 7434 AN: 41432

American (AMR) AF: 0.0528 AC: 807 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 370 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5166

South Asian (SAS) AF: 0.0577 AC: 278 AN: 4814

European-Finnish (FIN) AF: 0.0466 AC: 492 AN: 10552

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0493 AC: 3352 AN: 67926

Other (OTH) AF: 0.0726 AC: 153 AN: 2106

Alfa AF: 0.0689 Hom.: 97

Bravo AF: 0.0888

Asia WGS AF: 0.0310 AC: 108 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.56
PhyloP100		-0.076
Mutation Taster		=100/0	polymorphism (auto)

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: rs12318506; hg19: chr12-75718423;