Variant 19-5914639-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004058.5(CAPS):c.160G>A(p.Gly54Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0015 in 1,614,014 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 38 hom. )

Consequence

CAPS
NM_004058.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.68

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:

CAPS (HGNC:):

CAPS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010447592).

BP6

Variant 19-5914639-G-A is Benign according to our data. Variant chr19-5914639-G-A is described in ClinVar as [Benign]. Clinvar id is 3043545.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00149 (2180/1461660) while in subpopulation SAS AF= 0.02 (1727/86250). AF 95% confidence interval is 0.0192. There are 38 homozygotes in gnomad4_exome. There are 1485 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPS	NM_004058.5 linkuse as main transcript	c.160G>A	p.Gly54Arg	missense_variant	3/5	ENST00000588776.8	NP_004049.3	Q13938-4A0A384NYV7Q96ET4
CAPS	NM_080590.4 linkuse as main transcript	c.160G>A	p.Gly54Arg	missense_variant	3/5		NP_542157.3	Q13938

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAPS	ENST00000588776.8 linkuse as main transcript	c.160G>A	p.Gly54Arg	missense_variant	3/5	1	NM_004058.5	ENSP00000465883.2	Q13938-4
ENSG00000267314	ENST00000588891.1 linkuse as main transcript	n.*255G>A		non_coding_transcript_exon_variant	4/4	4		ENSP00000468419.1	K7ERU9
ENSG00000267314	ENST00000588891.1 linkuse as main transcript	n.*255G>A		3_prime_UTR_variant	4/4	4		ENSP00000468419.1	K7ERU9

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00311

AC:

780

AN:

250698

Hom.:

AF XY:

0.00412

AC XY:

559

AN XY:

135658

show subpopulations

Gnomad AFR exome

AF:

0.000864

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000597

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.0209

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00149

AC:

2180

AN:

1461660

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

1485

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.0200

Gnomad4 FIN exome

AF:

0.0000939

Gnomad4 NFE exome

AF:

0.000150

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00156

AC:

237

AN:

152354

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00120

Hom.:

Bravo

AF:

0.000967

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00347

AC:

421

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CAPS-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 17, 2020

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

Uncertain

0.51

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

.;.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

T;T;T

MetaRNN

Benign

0.010

T;T;T

MetaSVM

Uncertain

0.52

PrimateAI

Uncertain

0.54

REVEL

Pathogenic

0.70

Sift4G

Uncertain

0.0020

D;D;D

Vest4

0.72

MutPred

0.67

.;.;Gain of solvent accessibility (P = 0.0471);

MVP

0.88

ClinPred

0.061

GERP RS

5.0

Varity_R

0.50

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