chr17-80202245-C-T

Position:

chr17-80202245-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP3BP4_StrongBP6_Very_StrongBS1BS2

The NM_001366385.1(CARD14):c.2044C>T(p.Arg682Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,614,026 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 10 hom., cov: 32)

Exomes 𝑓: 0.014 ( 203 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 7.57

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:

ENSG00000262580 (HGNC:):

ENSG00000262580 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 7: Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.009360939).

BP6

Variant 17-80202245-C-T is Benign according to our data. Variant chr17-80202245-C-T is described in ClinVar as [Benign]. Clinvar id is 68778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80202245-C-T is described in Lovd as [Pathogenic]. Variant chr17-80202245-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0108 (1646/152310) while in subpopulation NFE AF= 0.0167 (1135/68022). AF 95% confidence interval is 0.0159. There are 10 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1646 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.2044C>T	p.Arg682Trp	missense_variant	18/24	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.2044C>T	p.Arg682Trp	missense_variant	18/24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1647

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00335

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00746

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00496

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0167

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0111

AC:

2802

AN:

251360

Hom.:

AF XY:

0.0114

AC XY:

1547

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00668

Gnomad ASJ exome

AF:

0.0158

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00663

Gnomad FIN exome

AF:

0.0145

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.0144

AC:

21075

AN:

1461716

Hom.:

203

Cov.:

AF XY:

0.0144

AC XY:

10460

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.00695

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00621

Gnomad4 FIN exome

AF:

0.0166

Gnomad4 NFE exome

AF:

0.0159

Gnomad4 OTH exome

AF:

0.0139

GnomAD4 genome

AF:

0.0108

AC:

1646

AN:

152310

Hom.:

Cov.:

AF XY:

0.00987

AC XY:

735

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00334

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.0132

Gnomad4 NFE

AF:

0.0167

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.00986

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0182

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0176

AC:

151

ExAC

AF:

0.0110

AC:

1337

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0163

EpiControl

AF:

0.0180

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

not provided, no classification provided	literature only	UniProtKB/Swiss-Prot	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	CARD14: BS1, BS2; ENSG00000262580: BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Autoinflammatory syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Mar 12, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.38

T;T;.;T

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

.;.;T;T

MetaRNN

Benign

0.0094

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.2

M;M;M;M

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.5

.;.;.;D

REVEL

Uncertain

0.35

Sift

Pathogenic

0.0

.;.;.;D

Sift4G

Pathogenic

0.0010

D;.;D;D

Polyphen

1.0

D;D;.;D

Vest4

0.30

MPC

0.66

ClinPred

0.043

GERP RS

4.9

Varity_R

0.81

gMVP

0.71

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