7-2930055-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032415.7(CARD11):c.1590A>C(p.Glu530Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,613,792 control chromosomes in the GnomAD database, including 280 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 159 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 121 hom. )

Consequence

CARD11
NM_032415.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -1.63

Publications

8 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018115938).

BP6

Variant 7-2930055-T-G is Benign according to our data. Variant chr7-2930055-T-G is described in ClinVar as Benign. ClinVar VariationId is 133784.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0824 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD11	NM_032415.7	MANE Select	c.1590A>C	p.Glu530Asp	missense	Exon 12 of 25	NP_115791.3
	CARD11	NM_001324281.3		c.1590A>C	p.Glu530Asp	missense	Exon 13 of 26	NP_001311210.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CARD11	ENST00000396946.9	TSL:1 MANE Select	c.1590A>C	p.Glu530Asp	missense	Exon 12 of 25	ENSP00000380150.4
CARD11	ENST00000355508.3	TSL:3	c.6A>C	p.Glu2Asp	missense	Exon 1 of 7	ENSP00000347695.3
CARD11	ENST00000698637.1		n.1916A>C		non_coding_transcript_exon	Exon 12 of 24

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3698

AN:

152090

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0847

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0182

GnomAD2 exomes

AF:

0.00651

AC:

1636

AN:

251178

AF XY:

0.00474

show subpopulations

Gnomad AFR exome

AF:

0.0884

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00249

AC:

3645

AN:

1461582

Hom.:

121

Cov.:

AF XY:

0.00219

AC XY:

1589

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.0855

AC:

2861

AN:

33470

American (AMR)

AF:

0.00452

AC:

202

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000197

AC:

219

AN:

1111800

Other (OTH)

AF:

0.00505

AC:

305

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

161

322

482

643

804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.0244

AC:

3708

AN:

152210

Hom.:

159

Cov.:

AF XY:

0.0230

AC XY:

1714

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0847

AC:

3514

AN:

41494

American (AMR)

AF:

0.00804

AC:

123

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000412

AC:

AN:

68000

Other (OTH)

AF:

0.0180

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

171

342

512

683

854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00892

Hom.:

122

Bravo

AF:

0.0280

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0903

AC:

398

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00777

AC:

943

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.052

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.10

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

PhyloP100

-1.6

PrimateAI

Benign

0.32

PROVEAN

Benign

0.26

REVEL

Benign

0.011

Sift

Benign

0.89

Sift4G

Benign

0.92

Polyphen

0.0

Vest4

0.089

MutPred

0.092

Gain of helix (P = 0.0696)

MVP

0.28

MPC

0.40

ClinPred

0.0040

GERP RS

-5.4

PromoterAI

0.018

Neutral

(source)

Varity_R

0.023

gMVP

0.14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over