rs1621509

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.1599C>T(p.Asp533Asp) 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

Publications

27 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=-0.87).

BP6

Variant 7-2930046-G-A is Benign according to our data. Variant chr7-2930046-G-A is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
CARD11	NM_032415.7 link	c.1599C>T	p.Asp533Asp	synonymous_variant	Exon 12 of 25	ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3 link	c.1599C>T	p.Asp533Asp	synonymous_variant	Exon 13 of 26		NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CARD11	ENST00000396946.9 link	c.1599C>T	p.Asp533Asp	synonymous_variant	Exon 12 of 25	1	NM_032415.7	ENSP00000380150.4
CARD11	ENST00000355508.3 link	c.15C>T	p.Asp5Asp	synonymous_variant	Exon 1 of 7	3		ENSP00000347695.3
CARD11	ENST00000698637.1 link	n.1925C>T		non_coding_transcript_exon_variant	Exon 12 of 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

GnomAD2 exomes

AF:

0.190

AC:

47762

AN:

251042

AF XY:

0.189

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 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

African (AFR)

AF:

0.0678

AC:

2270

AN:

33470

American (AMR)

AF:

0.231

AC:

10317

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4511

AN:

26118

East Asian (EAS)

AF:

0.0125

AC:

496

AN:

39692

South Asian (SAS)

AF:

0.124

AC:

10679

AN:

86216

European-Finnish (FIN)

AF:

0.281

AC:

14995

AN:

53372

Middle Eastern (MID)

AF:

0.236

AC:

1360

AN:

5764

European-Non Finnish (NFE)

AF:

0.226

AC:

251411

AN:

1110974

Other (OTH)

AF:

0.195

AC:

11762

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

12303

24606

36908

49211

61514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8436

16872

25308

33744

42180

<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:

0.170

AC:

25832

AN:

152136

Hom.:

2634

Cov.:

AF XY:

0.169

AC XY:

12560

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0734

AC:

3047

AN:

41506

American (AMR)

AF:

0.182

AC:

2785

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

592

AN:

3472

East Asian (EAS)

AF:

0.00908

AC:

AN:

5178

South Asian (SAS)

AF:

0.110

AC:

530

AN:

4824

European-Finnish (FIN)

AF:

0.276

AC:

2927

AN:

10586

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.226

AC:

15334

AN:

67958

Other (OTH)

AF:

0.162

AC:

341

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1095

2190

3285

4380

5475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.202

Hom.:

14062

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

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 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. 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 -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.81

(source)

DANN

Benign

0.39

PhyloP100

-1.3

PromoterAI

-0.036

Neutral

(source)

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