rs6945582

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.1245C>T(p.Asp415Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,614,084 control chromosomes in the GnomAD database, including 27,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1956 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25733 hom. )

Consequence

CARD11
NM_032415.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.431

Publications

22 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=-0.51).

BP6

Variant 7-2937133-G-A is Benign according to our data. Variant chr7-2937133-G-A is described in ClinVar as Benign. ClinVar VariationId is 402481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.431 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD11	NM_032415.7 link	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 9 of 25	ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3 link	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 10 of 26		NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CARD11	ENST00000396946.9 link	c.1245C>T	p.Asp415Asp	synonymous_variant	Exon 9 of 25	1	NM_032415.7	ENSP00000380150.4
CARD11	ENST00000698637.1 link	n.1571C>T		non_coding_transcript_exon_variant	Exon 9 of 24
CARD11	ENST00000698654.1 link	n.1504C>T		non_coding_transcript_exon_variant	Exon 9 of 10
CARD11	ENST00000698662.1 link	n.1445C>T		non_coding_transcript_exon_variant	Exon 9 of 10

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22425

AN:

152130

Hom.:

1954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0728

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.00769

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.141

GnomAD2 exomes

AF:

0.164

AC:

41111

AN:

251382

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.0686

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.00414

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.181

AC:

264066

AN:

1461836

Hom.:

25733

Cov.:

AF XY:

0.179

AC XY:

130204

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0685

AC:

2295

AN:

33480

American (AMR)

AF:

0.200

AC:

8949

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

3079

AN:

26136

East Asian (EAS)

AF:

0.00290

AC:

115

AN:

39676

South Asian (SAS)

AF:

0.110

AC:

9461

AN:

86258

European-Finnish (FIN)

AF:

0.234

AC:

12473

AN:

53408

Middle Eastern (MID)

AF:

0.199

AC:

1145

AN:

5768

European-Non Finnish (NFE)

AF:

0.195

AC:

216574

AN:

1111992

Other (OTH)

AF:

0.165

AC:

9975

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13713

27427

41140

54854

68567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7380

14760

22140

29520

36900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.147

AC:

22430

AN:

152248

Hom.:

1956

Cov.:

AF XY:

0.147

AC XY:

10925

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0727

AC:

3022

AN:

41564

American (AMR)

AF:

0.156

AC:

2390

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

399

AN:

3466

East Asian (EAS)

AF:

0.00751

AC:

AN:

5190

South Asian (SAS)

AF:

0.0968

AC:

467

AN:

4822

European-Finnish (FIN)

AF:

0.233

AC:

2472

AN:

10600

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.193

AC:

13153

AN:

67984

Other (OTH)

AF:

0.139

AC:

294

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

994

1989

2983

3978

4972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

256

512

768

1024

1280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.132

Hom.:

1039

Bravo

AF:

0.139

Asia WGS

AF:

0.0640

AC:

224

AN:

3478

EpiCase

AF:

0.182

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

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: MAF -

BENTA disease

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;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

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.3

(source)

DANN

Benign

0.78

PhyloP100

-0.43

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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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