rs62074378

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001366385.1(CARD14):c.1371G>A(p.Ser457Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0416 in 1,608,020 control chromosomes in the GnomAD database, including 1,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S457S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.031 ( 101 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1483 hom. )

Consequence

CARD14
NM_001366385.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.07

Publications

0 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-80195205-G-A is Benign according to our data. Variant chr17-80195205-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 458086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.07 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0312 (4752/152242) while in subpopulation NFE AF = 0.0462 (3141/67990). AF 95% confidence interval is 0.0448. There are 101 homozygotes in GnomAd4. There are 2276 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4752 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.1371G>A	p.Ser457Ser	synonymous_variant	Exon 13 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.1371G>A	p.Ser457Ser	synonymous_variant	Exon 13 of 24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.0313

AC:

4755

AN:

152124

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00922

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0343

Gnomad FIN

AF:

0.0390

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.0335

GnomAD2 exomes

AF:

0.0339

AC:

8355

AN:

246688

AF XY:

0.0350

show subpopulations

Gnomad AFR exome

AF:

0.00947

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0365

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0373

Gnomad NFE exome

AF:

0.0474

Gnomad OTH exome

AF:

0.0361

GnomAD4 exome

AF:

0.0427

AC:

62161

AN:

1455778

Hom.:

1483

Cov.:

AF XY:

0.0425

AC XY:

30760

AN XY:

723478

show subpopulations

African (AFR)

AF:

0.00901

AC:

301

AN:

33394

American (AMR)

AF:

0.0191

AC:

852

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.0346

AC:

901

AN:

26054

East Asian (EAS)

AF:

0.000126

AC:

AN:

39602

South Asian (SAS)

AF:

0.0335

AC:

2882

AN:

86040

European-Finnish (FIN)

AF:

0.0376

AC:

1951

AN:

51824

Middle Eastern (MID)

AF:

0.0372

AC:

190

AN:

5106

European-Non Finnish (NFE)

AF:

0.0476

AC:

52828

AN:

1109074

Other (OTH)

AF:

0.0374

AC:

2251

AN:

60132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3337

6673

10010

13346

16683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1944

3888

5832

7776

9720

<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:

0.0312

AC:

4752

AN:

152242

Hom.:

101

Cov.:

AF XY:

0.0306

AC XY:

2276

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.00920

AC:

382

AN:

41542

American (AMR)

AF:

0.0300

AC:

458

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0291

AC:

101

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.0337

AC:

163

AN:

4832

European-Finnish (FIN)

AF:

0.0390

AC:

414

AN:

10612

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0462

AC:

3141

AN:

67990

Other (OTH)

AF:

0.0331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

239

478

716

955

1194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0279

Hom.:

Bravo

AF:

0.0294

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0458

EpiControl

AF:

0.0491

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Likely 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

- -

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

0.31

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.41

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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