NM_004058.5:c.53G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004058.5(CAPS):c.53G>A(p.Arg18His) variant causes a missense change. The variant allele was found at a frequency of 0.0131 in 1,612,424 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 14 hom., cov: 33)

Exomes 𝑓: 0.014 ( 177 hom. )

Consequence

CAPS
NM_004058.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.85

Publications

5 publications found

Variant links:

Genes affected

CAPS (HGNC:1487): (calcyphosine) This gene encodes a calcium-binding protein, which may play a role in the regulation of ion transport. A similar protein was first described as a potentially important regulatory protein in the dog thyroid and was termed as R2D5 antigen in rabbit. Alternative splicing of this gene generates two transcript variants. [provided by RefSeq, Jul 2008]

CAPS links:

ENSG00000267314 (HGNC:):

ENSG00000267314 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.009452552).

BP6

Variant 19-5914459-G-A is Benign according to our data. Variant chr19-5914459-G-A is described in ClinVar as [Benign]. Clinvar id is 781743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0136 (19907/1460126) while in subpopulation NFE AF = 0.016 (17785/1111432). AF 95% confidence interval is 0.0158. There are 177 homozygotes in GnomAdExome4. There are 9497 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPS	NM_004058.5 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 5	ENST00000588776.8	NP_004049.3	Q13938-4A0A384NYV7Q96ET4
CAPS	NM_080590.4 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 5		NP_542157.3	Q13938

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CAPS	ENST00000588776.8 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 5	1	NM_004058.5	ENSP00000465883.2	Q13938-4
ENSG00000267314	ENST00000588891.1 link	n.*148G>A		non_coding_transcript_exon_variant	Exon 3 of 4	4		ENSP00000468419.1	K7ERU9
ENSG00000267314	ENST00000588891.1 link	n.*148G>A		3_prime_UTR_variant	Exon 3 of 4	4		ENSP00000468419.1	K7ERU9

Frequencies

GnomAD3 genomes

AF:

0.00840

AC:

1278

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.0636

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00808

AC:

2020

AN:

250124

AF XY:

0.00812

show subpopulations

Gnomad AFR exome

AF:

0.00267

Gnomad AMR exome

AF:

0.00417

Gnomad ASJ exome

AF:

0.00878

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00630

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.00671

GnomAD4 exome

AF:

0.0136

AC:

19907

AN:

1460126

Hom.:

177

Cov.:

AF XY:

0.0131

AC XY:

9497

AN XY:

726202

show subpopulations

African (AFR)

AF:

0.00248

AC:

AN:

33462

American (AMR)

AF:

0.00389

AC:

174

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00808

AC:

211

AN:

26126

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39680

South Asian (SAS)

AF:

0.00422

AC:

364

AN:

86228

European-Finnish (FIN)

AF:

0.00737

AC:

386

AN:

52384

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0160

AC:

17785

AN:

1111432

Other (OTH)

AF:

0.0147

AC:

887

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1142

2285

3427

4570

5712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00838

AC:

1277

AN:

152298

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

563

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00315

AC:

131

AN:

41546

American (AMR)

AF:

0.00477

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00979

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00373

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00480

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0131

AC:

894

AN:

68014

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

131

197

262

328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.00802

TwinsUK

AF:

0.0162

AC:

ALSPAC

AF:

0.0161

AC:

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.0151

AC:

130

ExAC

AF:

0.00806

AC:

979

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0110

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

CAPS-related disorder

Benign:1

Aug 09, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.090

.;.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.76

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.0095

T;T;T

MetaSVM

Benign

-0.76

PhyloP100

4.9

PrimateAI

Uncertain

0.52

REVEL

Benign

0.22

Sift4G

Pathogenic

0.0010

D;D;D

Vest4

0.66

MVP

0.83

ClinPred

0.10

GERP RS

5.0

PromoterAI

-0.021

Neutral

(source)

Varity_R

0.32

Mutation Taster

=95/5

polymorphism

(source)

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

Publications

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NM_004058.5:c.53G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over