Genetic Variant NM_004058.5:c.160G>A (chr19-5914639-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 3043545.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 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 GnomAdExome4. There are 1485 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004058.5. 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
	CAPS	NM_004058.5	MANE Select	c.160G>A	p.Gly54Arg	missense	Exon 3 of 5	NP_004049.3	Q13938-4
	CAPS	NM_080590.4		c.160G>A	p.Gly54Arg	missense	Exon 3 of 5	NP_542157.3	A0A499FJ41

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CAPS	ENST00000588776.8	TSL:1 MANE Select	c.160G>A	p.Gly54Arg	missense	Exon 3 of 5	ENSP00000465883.2	Q13938-4
CAPS	ENST00000585541.1	TSL:1	n.293G>A		non_coding_transcript_exon	Exon 2 of 2
ENSG00000267314	ENST00000588891.1	TSL:4	n.*255G>A		non_coding_transcript_exon	Exon 4 of 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

GnomAD2 exomes

AF:

0.00311

AC:

780

AN:

250698

AF XY:

0.00412

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 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

African (AFR)

AF:

0.000299

AC:

AN:

33476

American (AMR)

AF:

0.00127

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000918

AC:

AN:

26134

East Asian (EAS)

AF:

0.000882

AC:

AN:

39696

South Asian (SAS)

AF:

0.0200

AC:

1727

AN:

86250

European-Finnish (FIN)

AF:

0.0000939

AC:

AN:

53258

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000150

AC:

167

AN:

1111966

Other (OTH)

AF:

0.00242

AC:

146

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

134

268

402

536

670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00156

AC:

237

AN:

152354

Hom.:

Cov.:

AF XY:

0.00187

AC XY:

139

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000673

AC:

AN:

41590

American (AMR)

AF:

0.00412

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5178

South Asian (SAS)

AF:

0.0174

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68034

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00129

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

ClinVar submissions as Germline

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CAPS-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

MetaRNN

Benign

0.010

MetaSVM

Uncertain

0.52

PhyloP100

4.7

PrimateAI

Uncertain

0.54

REVEL

Pathogenic

0.70

Sift4G

Uncertain

0.0020

Vest4

0.72

MutPred

0.67

Gain of solvent accessibility (P = 0.0471)

MVP

0.88

ClinPred

0.061

GERP RS

5.0

PromoterAI

-0.0066

Neutral

(source)

Varity_R

0.50

Mutation Taster

=73/27

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over