rs11653893

chr17-80205031-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001366385.1(CARD14):c.2399-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,571,222 control chromosomes in the GnomAD database, including 180,221 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign,association (★★).

Frequency

Genomes: 𝑓 0.40 ( 13255 hom., cov: 32)

Exomes 𝑓: 0.48 ( 166966 hom. )

Consequence

CARD14
NM_001366385.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003429

Clinical Significance

Benign; association criteria provided, multiple submitters, no conflicts B:5O:2

Conservation

PhyloP100: -0.517

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-80205031-A-G is Benign according to our data. Variant chr17-80205031-A-G is described in ClinVar as [Benign, association]. Clinvar id is 402486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80205031-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD14	NM_001366385.1 linkuse as main transcript	c.2399-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000648509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD14	ENST00000648509.2 linkuse as main transcript	c.2399-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001366385.1	P1	Q9BXL6-1
	ENST00000570309.1 linkuse as main transcript	n.41T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61288

AN:

151884

Hom.:

13256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.252

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.509

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.500

Gnomad OTH

AF:

0.408

GnomAD3 exomes

AF:

0.412

AC:

87216

AN:

211618

Hom.:

18785

AF XY:

0.420

AC XY:

48336

AN XY:

114984

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.433

Gnomad EAS exome

AF:

0.481

Gnomad SAS exome

AF:

0.341

Gnomad FIN exome

AF:

0.420

Gnomad NFE exome

AF:

0.489

Gnomad OTH exome

AF:

0.439

GnomAD4 exome

AF:

0.479

AC:

680308

AN:

1419220

Hom.:

166966

Cov.:

AF XY:

0.476

AC XY:

334090

AN XY:

701426

show subpopulations

Gnomad4 AFR exome

AF:

0.242

Gnomad4 AMR exome

AF:

0.275

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.559

Gnomad4 SAS exome

AF:

0.343

Gnomad4 FIN exome

AF:

0.430

Gnomad4 NFE exome

AF:

0.507

Gnomad4 OTH exome

AF:

0.453

GnomAD4 genome

AF:

0.403

AC:

61288

AN:

152002

Hom.:

13255

Cov.:

AF XY:

0.399

AC XY:

29683

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.251

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.430

Gnomad4 NFE

AF:

0.500

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.444

Hom.:

5999

Bravo

AF:

0.389

Asia WGS

AF:

0.389

AC:

1352

AN:

3478

ClinVar

Significance: Benign; association

Submissions summary: Benign:5Other:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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 53% of patients studied by a panel of primary immunodeficiencies. Number of patients: 51. 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 -

Pityriasis rubra pilaris

Benign:1Other:1

association, 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. rs11653893 variant is associated with Psoriasis . However, more studies are required to ascertain the role of rs11653893 in Psoriasis -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

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

Invitae

Feb 01, 2024

- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

0.067

Dann

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000034

dbscSNV1_RF

Benign

0.0

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

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