rs1124581

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

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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032415.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD11	NM_032415.7	MANE Select	c.3276A>G	p.Arg1092Arg	synonymous	Exon 25 of 25	NP_115791.3
	CARD11	NM_001324281.3		c.3276A>G	p.Arg1092Arg	synonymous	Exon 26 of 26	NP_001311210.1	Q9BXL7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARD11	ENST00000396946.9	TSL:1 MANE Select	c.3276A>G	p.Arg1092Arg	synonymous	Exon 25 of 25	ENSP00000380150.4	Q9BXL7
CARD11	ENST00000888804.1		c.3276A>G	p.Arg1092Arg	synonymous	Exon 25 of 25	ENSP00000558863.1
CARD11	ENST00000888805.1		c.3276A>G	p.Arg1092Arg	synonymous	Exon 25 of 25	ENSP00000558864.1

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

16184

32368

48552

64736

80920

<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:

0.544

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.513

Hom.:

54434

Bravo

AF:

0.555

Asia WGS

AF:

0.621

AC:

2160

AN:

3478

EpiCase

AF:

0.495

EpiControl

AF:

0.494

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

BENTA disease (1)

Immunodeficiency 11b with atopic dermatitis (1)

Severe combined immunodeficiency due to CARD11 deficiency (1)

Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over