17-80192527-G-A

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.1264G>A(p.Glu422Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 1,613,618 control chromosomes in the GnomAD database, including 763 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E422D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.022 ( 58 hom., cov: 33)

Exomes 𝑓: 0.029 ( 705 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.19

Publications

11 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=0.0033420026).

BP6

Variant 17-80192527-G-A is Benign according to our data. Variant chr17-80192527-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 458085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.1264G>A	p.Glu422Lys	missense_variant	Exon 12 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.1264G>A	p.Glu422Lys	missense_variant	Exon 12 of 24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3289

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00610

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.0218

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0329

Gnomad OTH

AF:

0.0268

GnomAD2 exomes

AF:

0.0228

AC:

5728

AN:

250914

AF XY:

0.0234

show subpopulations

Gnomad AFR exome

AF:

0.00532

Gnomad AMR exome

AF:

0.0180

Gnomad ASJ exome

AF:

0.0317

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0212

Gnomad NFE exome

AF:

0.0333

Gnomad OTH exome

AF:

0.0343

GnomAD4 exome

AF:

0.0294

AC:

43027

AN:

1461290

Hom.:

705

Cov.:

AF XY:

0.0294

AC XY:

21336

AN XY:

726938

show subpopulations

African (AFR)

AF:

0.00571

AC:

191

AN:

33474

American (AMR)

AF:

0.0188

AC:

842

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0325

AC:

849

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00859

AC:

741

AN:

86242

European-Finnish (FIN)

AF:

0.0218

AC:

1158

AN:

53158

Middle Eastern (MID)

AF:

0.0583

AC:

336

AN:

5768

European-Non Finnish (NFE)

AF:

0.0334

AC:

37182

AN:

1111728

Other (OTH)

AF:

0.0286

AC:

1727

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

1926

3853

5779

7706

9632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1358

2716

4074

5432

6790

<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:

0.0216

AC:

3288

AN:

152328

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1502

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00608

AC:

253

AN:

41580

American (AMR)

AF:

0.0184

AC:

282

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00684

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0218

AC:

232

AN:

10620

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0329

AC:

2235

AN:

68024

Other (OTH)

AF:

0.0265

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

166

332

498

664

830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0299

Hom.:

240

Bravo

AF:

0.0216

TwinsUK

AF:

0.0332

AC:

123

ALSPAC

AF:

0.0348

AC:

134

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.0292

AC:

251

ExAC

AF:

0.0228

AC:

2768

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0345

EpiControl

AF:

0.0359

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 32199921) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Autoinflammatory syndrome

Benign:1

Jan 22, 2022

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

0.087

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;T;.;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.68

.;.;T;T

MetaRNN

Benign

0.0033

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;M;M

PhyloP100

2.2

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

.;.;.;N

REVEL

Benign

0.033

Sift

Benign

0.10

.;.;.;T

Sift4G

Benign

0.22

T;.;T;T

Polyphen

0.88

P;P;.;P

Vest4

0.12

MPC

0.31

ClinPred

0.0051

GERP RS

3.6

Varity_R

0.12

gMVP

0.25

Mutation Taster

=96/4

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