Variant 19-5914940-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000588776.8(CAPS):c.262C>A(p.Pro88Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00376 in 1,601,158 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 107 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 93 hom. )

Consequence

CAPS
ENST00000588776.8 missense, splice_region

Scores

Splicing: ADA: 0.7410

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.94

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:

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=0.0032804012).

BP6

Variant 19-5914940-C-A is Benign according to our data. Variant chr19-5914940-C-A is described in ClinVar as [Benign]. Clinvar id is 769950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAPS	NM_004058.5 linkuse as main transcript	c.262C>A	p.Pro88Thr	missense_variant, splice_region_variant	4/5	ENST00000588776.8	NP_004049.3
CAPS	NM_080590.4 linkuse as main transcript	c.262C>A	p.Pro88Thr	missense_variant, splice_region_variant	4/5		NP_542157.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAPS	ENST00000588776.8 linkuse as main transcript	c.262C>A	p.Pro88Thr	missense_variant, splice_region_variant	4/5	1	NM_004058.5	ENSP00000465883	P1	Q13938-4

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3133

AN:

152156

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0722

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00550

AC:

1299

AN:

236300

Hom.:

AF XY:

0.00390

AC XY:

505

AN XY:

129412

show subpopulations

Gnomad AFR exome

AF:

0.0741

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000497

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000558

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.00199

AC:

2889

AN:

1448884

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1197

AN XY:

721074

show subpopulations

Gnomad4 AFR exome

AF:

0.0703

Gnomad4 AMR exome

AF:

0.00401

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000734

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000541

Gnomad4 OTH exome

AF:

0.00381

GnomAD4 genome

AF:

0.0206

AC:

3131

AN:

152274

Hom.:

107

Cov.:

AF XY:

0.0197

AC XY:

1467

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0720

Gnomad4 AMR

AF:

0.00640

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.0165

Alfa

AF:

0.000644

Hom.:

Bravo

AF:

0.0233

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0624

AC:

274

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.00664

AC:

804

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

.;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-0.73

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.55

REVEL

Benign

0.26

Sift4G

Uncertain

0.0040

D;D;D

Vest4

0.67

MVP

0.84

ClinPred

0.092

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.74

dbscSNV1_RF

Benign

0.69

SpliceAI score (max)

0.010

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