dbSNP rs61741511: CAPS:p.Pro88Thr (chr19-5914940-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004058.5(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
NM_004058.5 missense, splice_region

Scores

Splicing: ADA: 0.7410

Clinical Significance

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

Conservation

PhyloP100: 6.94

Publications

3 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:

ENSG00000267571 (HGNC:):

ENSG00000267571 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

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.262C>A	p.Pro88Thr	missense splice_region	Exon 4 of 5	NP_004049.3	Q13938-4
	CAPS	NM_080590.4		c.262C>A	p.Pro88Thr	missense splice_region	Exon 4 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.262C>A	p.Pro88Thr	missense splice_region	Exon 4 of 5	ENSP00000465883.2	Q13938-4
CAPS	ENST00000585541.1	TSL:1	n.594C>A		non_coding_transcript_exon	Exon 2 of 2
CAPS	ENST00000961097.1		c.262C>A	p.Pro88Thr	missense splice_region	Exon 4 of 5	ENSP00000631156.1

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

GnomAD2 exomes

AF:

0.00550

AC:

1299

AN:

236300

AF XY:

0.00390

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 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

African (AFR)

AF:

0.0703

AC:

2352

AN:

33436

American (AMR)

AF:

0.00401

AC:

179

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25868

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.000734

AC:

AN:

85832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44020

Middle Eastern (MID)

AF:

0.00114

AC:

AN:

5268

European-Non Finnish (NFE)

AF:

0.0000541

AC:

AN:

1110040

Other (OTH)

AF:

0.00381

AC:

229

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

156

311

467

622

778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.0206

AC:

3131

AN:

152274

Hom.:

107

Cov.:

AF XY:

0.0197

AC XY:

1467

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0720

AC:

2992

AN:

41556

American (AMR)

AF:

0.00640

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68010

Other (OTH)

AF:

0.0165

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

147

293

440

586

733

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00251

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.73

PhyloP100

6.9

PrimateAI

Uncertain

0.55

REVEL

Benign

0.26

Sift4G

Uncertain

0.0040

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

Mutation Taster

=38/62

polymorphism (auto)

(source)

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

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