rs34367357

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1753G>A(p.Val585Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,613,510 control chromosomes in the GnomAD database, including 5,603 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,association (★★). Synonymous variant affecting the same amino acid position (i.e. V585V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.067 ( 403 hom., cov: 32)

Exomes 𝑓: 0.081 ( 5200 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Benign; association criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.173

Publications

23 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=0.001291275).

BP6

Variant 17-80198493-G-A is Benign according to our data. Variant chr17-80198493-G-A is described in ClinVar as Benign|association. ClinVar VariationId is 1167399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.1753G>A	p.Val585Ile	missense_variant	Exon 16 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.1753G>A	p.Val585Ile	missense_variant	Exon 16 of 24		NM_001366385.1	ENSP00000498071.1

Frequencies

GnomAD3 genomes

AF:

0.0672

AC:

10222

AN:

152220

Hom.:

407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0401

Gnomad EAS

AF:

0.0823

Gnomad SAS

AF:

0.0874

Gnomad FIN

AF:

0.0607

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0778

Gnomad OTH

AF:

0.0670

GnomAD2 exomes

AF:

0.0872

AC:

21892

AN:

250978

AF XY:

0.0852

show subpopulations

Gnomad AFR exome

AF:

0.0300

Gnomad AMR exome

AF:

0.182

Gnomad ASJ exome

AF:

0.0398

Gnomad EAS exome

AF:

0.0822

Gnomad FIN exome

AF:

0.0632

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.0767

GnomAD4 exome

AF:

0.0807

AC:

117862

AN:

1461172

Hom.:

5200

Cov.:

AF XY:

0.0802

AC XY:

58326

AN XY:

726914

show subpopulations

African (AFR)

AF:

0.0275

AC:

921

AN:

33476

American (AMR)

AF:

0.174

AC:

7765

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0399

AC:

1042

AN:

26122

East Asian (EAS)

AF:

0.0860

AC:

3415

AN:

39694

South Asian (SAS)

AF:

0.0846

AC:

7295

AN:

86248

European-Finnish (FIN)

AF:

0.0635

AC:

3362

AN:

52924

Middle Eastern (MID)

AF:

0.0610

AC:

352

AN:

5768

European-Non Finnish (NFE)

AF:

0.0800

AC:

88989

AN:

1111852

Other (OTH)

AF:

0.0782

AC:

4721

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6844

13688

20533

27377

34221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3408

6816

10224

13632

17040

<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:

0.0671

AC:

10222

AN:

152338

Hom.:

403

Cov.:

AF XY:

0.0686

AC XY:

5112

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0305

AC:

1270

AN:

41582

American (AMR)

AF:

0.117

AC:

1798

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0401

AC:

139

AN:

3468

East Asian (EAS)

AF:

0.0823

AC:

427

AN:

5186

South Asian (SAS)

AF:

0.0873

AC:

421

AN:

4824

European-Finnish (FIN)

AF:

0.0607

AC:

645

AN:

10632

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0778

AC:

5290

AN:

68022

Other (OTH)

AF:

0.0663

AC:

140

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

503

1006

1508

2011

2514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0735

Hom.:

1004

Bravo

AF:

0.0689

TwinsUK

AF:

0.0707

AC:

262

ALSPAC

AF:

0.0810

AC:

312

ESP6500AA

AF:

0.0315

AC:

139

ESP6500EA

AF:

0.0691

AC:

594

ExAC

AF:

0.0835

AC:

10134

Asia WGS

AF:

0.0840

AC:

290

AN:

3478

ClinVar

Significance: Benign; association

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 32725812) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

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 22% of patients studied by a panel of primary immunodeficiencies. Number of patients: 21. Only high quality variants are reported. -

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

- -

Pityriasis rubra pilaris

Other:1

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance:association

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CARD14 is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Potent mutations in Card14 have been shown to be associated with familial pustular psoriasis and other cutaneous inflammatory conditions like Pytriasis rubra pilaris. Sufficient evidence is found to confer the association of this particular variant rs34367357 with psoriasis -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.31

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.0062

T;T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.58

.;.;T;T

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.21

N;N;N;N

PhyloP100

-0.17

PrimateAI

Benign

0.32

PROVEAN

Benign

0.25

.;.;.;N

REVEL

Benign

0.022

Sift

Benign

0.85

.;.;.;T

Sift4G

Benign

1.0

T;.;T;T

Polyphen

0.0060

B;B;.;B

Vest4

0.079

MPC

0.12

ClinPred

0.0011

GERP RS

-1.4

Varity_R

0.018

gMVP

0.088

Mutation Taster

=99/1

polymorphism (auto)

(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

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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