chr7-2906827-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032415.7(CARD11):c.3276A>G(p.Arg1092Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,612,394 control chromosomes in the GnomAD database, including 206,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23029 hom., cov: 33)

Exomes 𝑓: 0.50 ( 183751 hom. )

Consequence

CARD11
NM_032415.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.383

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

BENTA disease
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
immunodeficiency 11b with atopic dermatitis
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp, Ambry Genetics
severe combined immunodeficiency due to CARD11 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, Orphanet

CARD11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-2906827-T-C is Benign according to our data. Variant chr7-2906827-T-C is described in ClinVar as [Benign]. Clinvar id is 402477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.383 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD11	NM_032415.7 link	c.3276A>G	p.Arg1092Arg	synonymous_variant	Exon 25 of 25	ENST00000396946.9	NP_115791.3	Q9BXL7A0A024R854Q8TES3
CARD11	NM_001324281.3 link	c.3276A>G	p.Arg1092Arg	synonymous_variant	Exon 26 of 26		NP_001311210.1	Q9BXL7A0A024R854Q8TES3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CARD11	ENST00000396946.9 link	c.3276A>G	p.Arg1092Arg	synonymous_variant	Exon 25 of 25	1	NM_032415.7	ENSP00000380150.4	Q9BXL7
CARD11	ENST00000698637.1 link	n.4386A>G		non_coding_transcript_exon_variant	Exon 24 of 24
CARD11	ENST00000698652.1 link	n.2232A>G		non_coding_transcript_exon_variant	Exon 8 of 8

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82663

AN:

151966

Hom.:

22999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.453

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.536

GnomAD2 exomes

AF:

0.510

AC:

126307

AN:

247676

AF XY:

0.509

show subpopulations

Gnomad AFR exome

AF:

0.661

Gnomad AMR exome

AF:

0.498

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.644

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.484

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.499

AC:

729248

AN:

1460310

Hom.:

183751

Cov.:

AF XY:

0.500

AC XY:

363088

AN XY:

726452

show subpopulations

African (AFR)

AF:

0.663

AC:

22180

AN:

33460

American (AMR)

AF:

0.501

AC:

22312

AN:

44558

Ashkenazi Jewish (ASJ)

AF:

0.457

AC:

11933

AN:

26106

East Asian (EAS)

AF:

0.604

AC:

23961

AN:

39660

South Asian (SAS)

AF:

0.545

AC:

46929

AN:

86168

European-Finnish (FIN)

AF:

0.414

AC:

21918

AN:

52962

Middle Eastern (MID)

AF:

0.492

AC:

2801

AN:

5694

European-Non Finnish (NFE)

AF:

0.492

AC:

546754

AN:

1111384

Other (OTH)

AF:

0.505

AC:

30460

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

19656

39312

58968

78624

98280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.544

AC:

82741

AN:

152084

Hom.:

23029

Cov.:

AF XY:

0.542

AC XY:

40306

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.670

AC:

27788

AN:

41502

American (AMR)

AF:

0.528

AC:

8073

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.453

AC:

1570

AN:

3468

East Asian (EAS)

AF:

0.637

AC:

3281

AN:

5148

South Asian (SAS)

AF:

0.566

AC:

2727

AN:

4822

European-Finnish (FIN)

AF:

0.412

AC:

4363

AN:

10582

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33185

AN:

67946

Other (OTH)

AF:

0.542

AC:

1147

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1993

3986

5979

7972

9965

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.513

Hom.:

54434

Bravo

AF:

0.555

Asia WGS

AF:

0.621

AC:

2160

AN:

3478

EpiCase

AF:

0.495

EpiControl

AF:

0.494

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 29, 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 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

BENTA disease

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Immunodeficiency 11b with atopic dermatitis

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Severe combined immunodeficiency due to CARD11 deficiency

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Other:1

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

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

-0.67

CADD

Benign

5.3

(source)

DANN

Benign

0.36

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr7-2906827-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over