rs114218658

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001366385.1(CARD14):c.709A>C(p.Asn237His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,611,048 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00044 ( 5 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.102

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:

CARD14 (HGNC:):

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=0.0032362044).

BP6

Variant 17-80188410-A-C is Benign according to our data. Variant chr17-80188410-A-C is described in ClinVar as [Benign]. Clinvar id is 458108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80188410-A-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00413 (629/152364) while in subpopulation AFR AF= 0.0146 (609/41582). AF 95% confidence interval is 0.0137. There are 4 homozygotes in gnomad4. There are 322 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 629 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.709A>C	p.Asn237His	missense_variant	8/24	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2 linkuse as main transcript	c.709A>C	p.Asn237His	missense_variant	8/24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.00414

AC:

630

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00118

AC:

293

AN:

247368

Hom.:

AF XY:

0.000919

AC XY:

123

AN XY:

133846

show subpopulations

Gnomad AFR exome

AF:

0.0166

Gnomad AMR exome

AF:

0.000630

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000503

GnomAD4 exome

AF:

0.000442

AC:

645

AN:

1458684

Hom.:

Cov.:

AF XY:

0.000371

AC XY:

269

AN XY:

725568

show subpopulations

Gnomad4 AFR exome

AF:

0.0164

Gnomad4 AMR exome

AF:

0.000813

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000780

GnomAD4 genome

AF:

0.00413

AC:

629

AN:

152364

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

322

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.00472

ESP6500AA

AF:

0.0145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00149

AC:

181

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 25, 2022

- -

CARD14-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.5

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0092

T;T;.;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.65

.;.;T;T

MetaRNN

Benign

0.0032

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.82

.;.;.;N

REVEL

Benign

0.023

Sift

Benign

0.080

.;.;.;T

Sift4G

Uncertain

0.030

D;.;D;D

Polyphen

0.65

P;P;.;P

Vest4

0.26

MVP

0.58

MPC

0.22

ClinPred

0.0070

GERP RS

0.53

Varity_R

0.055

gMVP

0.058

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