rs1621509

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032415.7(CARD11):c.1599C>T(p.Asp533=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,612,744 control chromosomes in the GnomAD database, including 37,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2634 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34817 hom. )

Consequence

CARD11
NM_032415.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.30

Variant links:

Genes affected

CARD11 (HGNC:16393): (caspase recruitment domain family member 11) The protein encoded by this gene belongs to the membrane-associated guanylate kinase (MAGUK) family, a class of proteins that functions as molecular scaffolds for the assembly of multiprotein complexes at specialized regions of the plasma membrane. This protein is also a member of the CARD protein family, which is defined by carrying a characteristic caspase-associated recruitment domain (CARD). This protein has a domain structure similar to that of CARD14 protein. The CARD domains of both proteins have been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. When expressed in cells, this protein activated NF-kappaB and induced the phosphorylation of BCL10. [provided by RefSeq, Jul 2008]

CARD11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 7-2930046-G-A is Benign according to our data. Variant chr7-2930046-G-A is described in ClinVar as [Benign]. Clinvar id is 402480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD11	NM_032415.7 linkuse as main transcript	c.1599C>T	p.Asp533=	synonymous_variant	12/25	ENST00000396946.9
CARD11	NM_001324281.3 linkuse as main transcript	c.1599C>T	p.Asp533=	synonymous_variant	13/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CARD11	ENST00000396946.9 linkuse as main transcript	c.1599C>T	p.Asp533=	synonymous_variant	12/25	1	NM_032415.7	P1
CARD11	ENST00000355508.3 linkuse as main transcript	c.15C>T	p.Asp5=	synonymous_variant	1/7	3
CARD11	ENST00000698637.1 linkuse as main transcript	n.1925C>T		non_coding_transcript_exon_variant	12/24

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25834

AN:

152018

Hom.:

2632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0736

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.171

Gnomad EAS

AF:

0.00925

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.226

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.190

AC:

47762

AN:

251042

Hom.:

5426

AF XY:

0.189

AC XY:

25577

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0696

Gnomad AMR exome

AF:

0.239

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.00582

Gnomad SAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.280

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.208

GnomAD4 exome

AF:

0.211

AC:

307801

AN:

1460608

Hom.:

34817

Cov.:

AF XY:

0.209

AC XY:

151800

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.0678

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.173

Gnomad4 EAS exome

AF:

0.0125

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.281

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.195

GnomAD4 genome

AF:

0.170

AC:

25832

AN:

152136

Hom.:

2634

Cov.:

AF XY:

0.169

AC XY:

12560

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0734

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.171

Gnomad4 EAS

AF:

0.00908

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.226

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.208

Hom.:

6579

Bravo

AF:

0.160

Asia WGS

AF:

0.0710

AC:

249

AN:

3478

EpiCase

AF:

0.217

EpiControl

AF:

0.217

ClinVar

Significance: Benign

Submissions summary: Benign:6

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: MAF -
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 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

BENTA disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Immunodeficiency 11b with atopic dermatitis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Severe combined immunodeficiency due to CARD11 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

Cadd

Benign

0.81

Dann

Benign

0.39

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