chr19-5914639-G-A

Variant names:

• chr19-5914639-G-A
• rs199930097
• NM_004058.5:c.160G>A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.68

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]

ENSG00000267314 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
CAPS	NM_004058.5	c.160G>A	p.Gly54Arg	missense_variant	Exon 3 of 5	ENST00000588776.8	NP_004049.3
CAPS	NM_080590.4	c.160G>A	p.Gly54Arg	missense_variant	Exon 3 of 5		NP_542157.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPS	ENST00000588776.8	c.160G>A	p.Gly54Arg	missense_variant	Exon 3 of 5	1	NM_004058.5	ENSP00000465883.2
ENSG00000267314	ENST00000588891.1	n.*255G>A		non_coding_transcript_exon_variant	Exon 4 of 4	4		ENSP00000468419.1
ENSG00000267314	ENST00000588891.1	n.*255G>A		3_prime_UTR_variant	Exon 4 of 4	4		ENSP00000468419.1

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152236 Hom.: 2 Cov.: 33

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.: 12 AF XY: 0.00412 AC XY: 559 AN XY: 135658

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.: 38 Cov.: 33 AF XY: 0.00204 AC XY: 1485 AN XY: 727146

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.: 2 Cov.: 33 AF XY: 0.00187 AC XY: 139 AN XY: 74500

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.: 16

Bravo AF: 0.000967

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

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

Submissions by phenotype

CAPS-related disorder Benign:1

Feb 17, 2020

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	Uncertain	0.51
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.39	.;.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.84	T;T;T
MetaRNN	Benign	0.010	T;T;T
MetaSVM	Uncertain	0.52	D
PrimateAI	Uncertain	0.54	T
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	T
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

Other links and lift over

dbSNP: rs199930097; hg19: chr19-5914650;