rs8069255

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001257970.1(CARD14):c.*10T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 1,604,700 control chromosomes in the GnomAD database, including 184,171 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 0.40 ( 13277 hom., cov: 31)

Exomes 𝑓: 0.48 ( 170894 hom. )

Consequence

CARD14
NM_001257970.1 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.42

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:

SGSH (HGNC:10818): (N-sulfoglucosamine sulfohydrolase) This gene encodes the enzyme sulfamidase; one of several enzymes involved in the lysosomal degradation of heparan sulfate. Mutations in this gene are associated with the lysosomal storage disease mucopolysaccaridosis IIIA, also known as Sanfilippo syndrome A, which results from impaired degradation of heparan sulfate. Transcripts of varying sizes have been reported but their biological validity has not been determined. [provided by RefSeq, Jun 2017]

SGSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 17-80202434-T-A is Benign according to our data. Variant chr17-80202434-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 402482.We mark this variant Likely_benign, oryginal submissions are: {Benign=7, Uncertain_significance=1}. Variant chr17-80202434-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD14	NM_001366385.1 link	c.2219+14T>A		intron_variant	Intron 18 of 23	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2 link	c.2219+14T>A		intron_variant	Intron 18 of 23		NM_001366385.1	ENSP00000498071.1		Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61389

AN:

151768

Hom.:

13278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.413

Gnomad EAS

AF:

0.499

Gnomad SAS

AF:

0.322

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.501

Gnomad OTH

AF:

0.402

GnomAD3 exomes

AF:

0.414

AC:

101338

AN:

245052

Hom.:

22197

AF XY:

0.421

AC XY:

56076

AN XY:

133294

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.470

Gnomad SAS exome

AF:

0.331

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.479

AC:

695715

AN:

1452814

Hom.:

170894

Cov.:

AF XY:

0.476

AC XY:

342982

AN XY:

721196

show subpopulations

Gnomad4 AFR exome

AF:

0.246

Gnomad4 AMR exome

AF:

0.275

Gnomad4 ASJ exome

AF:

0.421

Gnomad4 EAS exome

AF:

0.550

Gnomad4 SAS exome

AF:

0.336

Gnomad4 FIN exome

AF:

0.431

Gnomad4 NFE exome

AF:

0.508

Gnomad4 OTH exome

AF:

0.454

GnomAD4 genome

AF:

0.404

AC:

61394

AN:

151886

Hom.:

13277

Cov.:

AF XY:

0.400

AC XY:

29687

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.337

Gnomad4 ASJ

AF:

0.413

Gnomad4 EAS

AF:

0.500

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.431

Gnomad4 NFE

AF:

0.501

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.373

Hom.:

1729

Bravo

AF:

0.400

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

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 rs8069255 is yet to be ascertained. -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 59. Only high quality variants are reported. -

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Psoriasis 2

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pityriasis rubra pilaris;C1864497:Psoriasis 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.17

DANN

Benign

0.26

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