17-80198145-G-C

Position:

chr17-80198145-G-C

Variant summary

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

The NM_001366385.1(CARD14):c.1641G>C(p.Arg547Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,612,916 control chromosomes in the GnomAD database, including 116,819 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 Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10054 hom., cov: 32)

Exomes 𝑓: 0.38 ( 106765 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0340

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=1.0025016E-4).

BP6

Variant 17-80198145-G-C is Benign according to our data. Variant chr17-80198145-G-C is described in ClinVar as [Benign]. Clinvar id is 402485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-80198145-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 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.1641G>C	p.Arg547Ser	missense_variant	15/24	ENST00000648509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD14	ENST00000648509.2 linkuse as main transcript	c.1641G>C	p.Arg547Ser	missense_variant	15/24		NM_001366385.1	P1	Q9BXL6-1

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54625

AN:

151870

Hom.:

10051

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.377

Gnomad AMR

AF:

0.303

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.431

Gnomad FIN

AF:

0.380

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.375

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.372

AC:

93363

AN:

251266

Hom.:

18158

AF XY:

0.382

AC XY:

51865

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.313

Gnomad AMR exome

AF:

0.227

Gnomad ASJ exome

AF:

0.498

Gnomad EAS exome

AF:

0.452

Gnomad SAS exome

AF:

0.439

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.379

AC:

553711

AN:

1460928

Hom.:

106765

Cov.:

AF XY:

0.383

AC XY:

278453

AN XY:

726792

show subpopulations

Gnomad4 AFR exome

AF:

0.319

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.510

Gnomad4 SAS exome

AF:

0.443

Gnomad4 FIN exome

AF:

0.380

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.383

GnomAD4 genome

AF:

0.360

AC:

54644

AN:

151988

Hom.:

10054

Cov.:

AF XY:

0.358

AC XY:

26593

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.315

Gnomad4 AMR

AF:

0.302

Gnomad4 ASJ

AF:

0.509

Gnomad4 EAS

AF:

0.466

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.380

Gnomad4 NFE

AF:

0.375

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.385

Hom.:

8667

Bravo

AF:

0.350

TwinsUK

AF:

0.382

AC:

1418

ALSPAC

AF:

0.372

AC:

1435

ESP6500AA

AF:

0.313

AC:

1379

ESP6500EA

AF:

0.383

AC:

3292

ExAC

AF:

0.377

AC:

45771

Asia WGS

AF:

0.434

AC:

1511

AN:

3478

EpiCase

AF:

0.392

EpiControl

AF:

0.395

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 -
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 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 49. Only high quality variants are reported. -

not provided

Benign:1Other: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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Pityriasis rubra pilaris

Benign:1

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.6

DANN

Benign

0.64

DEOGEN2

Benign

0.0031

T;T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0011

MetaRNN

Benign

0.00010

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.1

N;N;N;N

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.30

Sift4G

Benign

0.83

T;.;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.015

MutPred

0.31

Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);

MPC

0.17

ClinPred

0.0040

GERP RS

0.71

Varity_R

0.074

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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