rs34367357

chr17-80198493-G-A

Variant summary

Our verdict is Benign. Variant got -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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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:3O:1

Conservation

PhyloP100: -0.173

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 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=0.001291275).

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 id 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/exons	MANE	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.1753G>A	p.Val585Ile	missense_variant	16/24	ENST00000648509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD14	ENST00000648509.2 linkuse as main transcript	c.1753G>A	p.Val585Ile	missense_variant	16/24		NM_001366385.1	P1	Q9BXL6-1

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

GnomAD3 exomes

AF:

0.0872

AC:

21892

AN:

250978

Hom.:

1229

AF XY:

0.0852

AC XY:

11567

AN XY:

135788

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 SAS exome

AF:

0.0853

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

Gnomad4 AFR exome

AF:

0.0275

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.0399

Gnomad4 EAS exome

AF:

0.0860

Gnomad4 SAS exome

AF:

0.0846

Gnomad4 FIN exome

AF:

0.0635

Gnomad4 NFE exome

AF:

0.0800

Gnomad4 OTH exome

AF:

0.0782

GnomAD4 genome

AF:

0.0671

AC:

10222

AN:

152338

Hom.:

403

Cov.:

AF XY:

0.0686

AC XY:

5112

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0305

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.0401

Gnomad4 EAS

AF:

0.0823

Gnomad4 SAS

AF:

0.0873

Gnomad4 FIN

AF:

0.0607

Gnomad4 NFE

AF:

0.0778

Gnomad4 OTH

AF:

0.0663

Alfa

AF:

0.0754

Hom.:

754

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:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

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

Pityriasis rubra pilaris

Other:1

association, criteria provided, single submitter

clinical testing

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

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

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

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.21

N;N;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.32

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

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

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