rs114688446

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.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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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=0.003829211).

BP6

Variant 17-80184162-G-A is Benign according to our data. Variant chr17-80184162-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 68785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80184162-G-A is described in Lovd as [Pathogenic]. Variant chr17-80184162-G-A is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 904 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.599G>A	p.Ser200Asn	missense_variant	7/24	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.599G>A	p.Ser200Asn	missense_variant	7/24		NM_001366385.1	ENSP00000498071	P1	Q9BXL6-1

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

GnomAD3 exomes

AF:

0.00640

AC:

1095

AN:

171110

Hom.:

AF XY:

0.00677

AC XY:

616

AN XY:

90974

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 SAS exome

AF:

0.00824

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

Gnomad4 AFR exome

AF:

0.000897

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.0193

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00821

Gnomad4 FIN exome

AF:

0.00551

Gnomad4 NFE exome

AF:

0.00787

Gnomad4 OTH exome

AF:

0.00926

GnomAD4 genome

AF:

0.00594

AC:

904

AN:

152274

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

429

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00746

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.00879

Gnomad4 OTH

AF:

0.00380

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	UniProtKB/Swiss-Prot	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	CARD14: BP4, BS2 -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 30, 2024

- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 05, 2022

- -

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

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

MutationTaster

Benign

1.0

N;N;N

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

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