Variant 19-5914459-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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. gnomad4_exome 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 gnomad4_exome. There are 9497 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 gene

Transcripts

RefSeq

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

Ensembl

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

GnomAD3 exomes

AF:

0.00808

AC:

2020

AN:

250124

Hom.:

AF XY:

0.00812

AC XY:

1100

AN XY:

135504

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 SAS exome

AF:

0.00445

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

Gnomad4 AFR exome

AF:

0.00248

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00808

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00422

Gnomad4 FIN exome

AF:

0.00737

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.00838

AC:

1277

AN:

152298

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

563

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00315

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.0131

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0115

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CAPS-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 09, 2019

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

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

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

Varity_R

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over