chr17-80198145-G-C

Variant names:

Variant summary

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

The NM_001366385.1(CARD14):c.1641G>C(p.Arg547Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,612,916 control chromosomes in the GnomAD database, including 116,819 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R547R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.36 ( 10054 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106765 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.0340

Publications

42 publications found

Variant links:

Genes affected

CARD14 (HGNC:16446): (caspase recruitment domain family member 14) This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. Members of this protein family are scaffold proteins that are involved in a diverse array of cellular processes including cellular adhesion, signal transduction and cell polarity control. This protein has been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

CARD14 Gene-Disease associations (from GenCC):

familial pityriasis rubra pilaris
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
psoriasis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

CARD14 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=1.0025016E-4).

BP6

Variant 17-80198145-G-C is Benign according to our data. Variant chr17-80198145-G-C is described in ClinVar as Benign. ClinVar VariationId is 402485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.1641G>C	p.Arg547Ser	missense_variant	Exon 15 of 24	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2 link	c.1641G>C	p.Arg547Ser	missense_variant	Exon 15 of 24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54625

AN:

151870

Hom.:

10051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.357

GnomAD2 exomes

AF:

0.372

AC:

93363

AN:

251266

AF XY:

0.382

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.498

Gnomad EAS exome

AF:

0.452

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.379

AC:

553711

AN:

1460928

Hom.:

106765

Cov.:

AF XY:

0.383

AC XY:

278453

AN XY:

726792

show subpopulations

African (AFR)

AF:

0.319

AC:

10654

AN:

33430

American (AMR)

AF:

0.236

AC:

10548

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.496

AC:

12950

AN:

26092

East Asian (EAS)

AF:

0.510

AC:

20258

AN:

39688

South Asian (SAS)

AF:

0.443

AC:

38158

AN:

86228

European-Finnish (FIN)

AF:

0.380

AC:

20187

AN:

53186

Middle Eastern (MID)

AF:

0.514

AC:

2942

AN:

5724

European-Non Finnish (NFE)

AF:

0.373

AC:

414887

AN:

1111500

Other (OTH)

AF:

0.383

AC:

23127

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

16656

33312

49969

66625

83281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13174

26348

39522

52696

65870

<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:

0.360

AC:

54644

AN:

151988

Hom.:

10054

Cov.:

AF XY:

0.358

AC XY:

26593

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.315

AC:

13058

AN:

41476

American (AMR)

AF:

0.302

AC:

4612

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

1745

AN:

3428

East Asian (EAS)

AF:

0.466

AC:

2405

AN:

5160

South Asian (SAS)

AF:

0.431

AC:

2078

AN:

4822

European-Finnish (FIN)

AF:

0.380

AC:

4024

AN:

10586

Middle Eastern (MID)

AF:

0.514

AC:

151

AN:

294

European-Non Finnish (NFE)

AF:

0.375

AC:

25469

AN:

67940

Other (OTH)

AF:

0.361

AC:

760

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1808

3616

5424

7232

9040

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.385

Hom.:

8667

Bravo

AF:

0.350

TwinsUK

AF:

0.382

AC:

1418

ALSPAC

AF:

0.372

AC:

1435

ESP6500AA

AF:

0.313

AC:

1379

ESP6500EA

AF:

0.383

AC:

3292

ExAC

AF:

0.377

AC:

45771

Asia WGS

AF:

0.434

AC:

1511

AN:

3478

EpiCase

AF:

0.392

EpiControl

AF:

0.395

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Pityriasis rubra pilaris

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Psoriasis 2

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.6

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.0031

T;T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.19

.;.;T;T

MetaRNN

Benign

0.00010

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.1

N;N;N;N

PhyloP100

0.034

PrimateAI

Benign

0.30

PROVEAN

Benign

0.44

.;.;.;N

REVEL

Benign

0.019

Sift

Benign

0.59

.;.;.;T

Sift4G

Benign

0.83

T;.;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.015

MutPred

0.31

Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);

MPC

0.17

ClinPred

0.0040

GERP RS

0.71

Varity_R

0.074

gMVP

0.23

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over