rs114688446

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_StrongBS1BS2

The NM_001366385.1(CARD14):c.599G>A(p.Ser200Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,563,970 control chromosomes in the GnomAD database, including 74 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 Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S200I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0059 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0076 ( 68 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.279

Publications

10 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=0.003829211).

BP6

Variant 17-80184162-G-A is Benign according to our data. Variant chr17-80184162-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 68785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00594 (904/152274) while in subpopulation NFE AF = 0.00879 (598/68016). AF 95% confidence interval is 0.00821. There are 6 homozygotes in GnomAd4. There are 429 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 904 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.599G>A	p.Ser200Asn	missense_variant	Exon 7 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.599G>A	p.Ser200Asn	missense_variant	Exon 7 of 24		NM_001366385.1	ENSP00000498071.1

Frequencies

GnomAD3 genomes

AF:

0.00595

AC:

905

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00766

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00879

Gnomad OTH

AF:

0.00384

GnomAD2 exomes

AF:

0.00640

AC:

1095

AN:

171110

AF XY:

0.00677

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00518

Gnomad NFE exome

AF:

0.00788

Gnomad OTH exome

AF:

0.00601

GnomAD4 exome

AF:

0.00755

AC:

10661

AN:

1411696

Hom.:

Cov.:

AF XY:

0.00766

AC XY:

5345

AN XY:

697442

show subpopulations

African (AFR)

AF:

0.000897

AC:

AN:

32334

American (AMR)

AF:

0.00224

AC:

AN:

37022

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

487

AN:

25226

East Asian (EAS)

AF:

0.00

AC:

AN:

36964

South Asian (SAS)

AF:

0.00821

AC:

657

AN:

79976

European-Finnish (FIN)

AF:

0.00551

AC:

273

AN:

49578

Middle Eastern (MID)

AF:

0.00762

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00787

AC:

8547

AN:

1086424

Other (OTH)

AF:

0.00926

AC:

542

AN:

58526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

578

1155

1733

2310

2888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.00594

AC:

904

AN:

152274

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

429

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

41556

American (AMR)

AF:

0.00516

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00746

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00518

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00879

AC:

598

AN:

68016

Other (OTH)

AF:

0.00380

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

136

182

227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00650

Hom.:

Bravo

AF:

0.00544

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00675

AC:

ExAC

AF:

0.00473

AC:

558

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CARD14: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

UniProtKB/Swiss-Prot

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autoinflammatory syndrome

Benign:1

Mar 05, 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

0.097

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.028

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.0048

T;T;.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.55

.;.;T;T

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.025

N;N;N;N

PhyloP100

-0.28

PrimateAI

Benign

0.44

PROVEAN

Benign

1.3

.;.;.;N

REVEL

Benign

0.019

Sift

Benign

1.0

.;.;.;T

Sift4G

Benign

1.0

T;.;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.044

MVP

0.40

MPC

0.14

ClinPred

0.00079

GERP RS

-3.7

Varity_R

0.033

gMVP

0.043

Mutation Taster

=99/1

polymorphism

(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