rs4889990

Positions:

chr17-80184196-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001366385.1(CARD14):c.633G>A(p.Glu211Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,554,468 control chromosomes in the GnomAD database, including 111,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.38 ( 11122 hom., cov: 33)

Exomes 𝑓: 0.38 ( 99952 hom. )

Consequence

CARD14
NM_001366385.1 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:7

Conservation

PhyloP100: 0.417

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 17-80184196-G-A is Benign according to our data. Variant chr17-80184196-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 402483.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=7}.

BP7

Synonymous conserved (PhyloP=0.417 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.633G>A	p.Glu211Glu	synonymous_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.633G>A	p.Glu211Glu	synonymous_variant	7/24		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57519

AN:

152016

Hom.:

11105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.375

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.356

AC:

58858

AN:

165328

Hom.:

10883

AF XY:

0.363

AC XY:

31967

AN XY:

88066

show subpopulations

Gnomad AFR exome

AF:

0.411

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.370

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.381

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.375

GnomAD4 exome

AF:

0.376

AC:

526613

AN:

1402334

Hom.:

99952

Cov.:

AF XY:

0.377

AC XY:

260820

AN XY:

691630

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.368

Gnomad4 EAS exome

AF:

0.234

Gnomad4 SAS exome

AF:

0.435

Gnomad4 FIN exome

AF:

0.387

Gnomad4 NFE exome

AF:

0.378

Gnomad4 OTH exome

AF:

0.374

GnomAD4 genome

AF:

0.378

AC:

57565

AN:

152134

Hom.:

11122

Cov.:

AF XY:

0.377

AC XY:

28048

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.306

Gnomad4 ASJ

AF:

0.369

Gnomad4 EAS

AF:

0.209

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.375

Gnomad4 NFE

AF:

0.383

Gnomad4 OTH

AF:

0.368

Alfa

AF:

0.381

Hom.:

18169

Bravo

AF:

0.371

Asia WGS

AF:

0.320

AC:

1117

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:7

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Pityriasis rubra pilaris

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	-	CARD14 is a scaffold protein that mediates NF-κB signal transduction in skin keratinocytes. Potent mutations in Card14 have been shown to be associated with familial pustular psoriasis and other cutaneous inflammatory conditions like Pytriasis rubra pilaris.However, the role of rs4889990 is yet to be ascertained. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 50% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Psoriasis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.4

DANN

Benign

0.49

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