chr7-2913281-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032415.7(CARD11):c.3019+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,591,864 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 18 hom. )

Consequence

CARD11
NM_032415.7 splice_region, intron

Scores

Splicing: ADA: 0.00009933

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.512

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-2913281-G-A is Benign according to our data. Variant chr7-2913281-G-A is described in ClinVar as Benign. ClinVar VariationId is 473932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00399 (602/150938) while in subpopulation AMR AF = 0.00962 (145/15070). AF 95% confidence interval is 0.00835. There are 4 homozygotes in GnomAd4. There are 271 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AD,AR gene

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.3019+6C>T		splice_region intron	N/A	NP_115791.3
	CARD11	NM_001324281.3		c.3019+6C>T		splice_region intron	N/A	NP_001311210.1	Q9BXL7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CARD11	ENST00000396946.9	TSL:1 MANE Select	c.3019+6C>T	splice_region intron	N/A	ENSP00000380150.4	Q9BXL7
CARD11	ENST00000888804.1		c.3019+6C>T	splice_region intron	N/A	ENSP00000558863.1
CARD11	ENST00000888805.1		c.3019+6C>T	splice_region intron	N/A	ENSP00000558864.1

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

603

AN:

150820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00970

Gnomad ASJ

AF:

0.00868

Gnomad EAS

AF:

0.00158

Gnomad SAS

AF:

0.000839

Gnomad FIN

AF:

0.00426

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00467

Gnomad OTH

AF:

0.00537

GnomAD2 exomes

AF:

0.00596

AC:

1408

AN:

236438

AF XY:

0.00510

show subpopulations

Gnomad AFR exome

AF:

0.000707

Gnomad AMR exome

AF:

0.0193

Gnomad ASJ exome

AF:

0.00593

Gnomad EAS exome

AF:

0.000442

Gnomad FIN exome

AF:

0.00535

Gnomad NFE exome

AF:

0.00487

Gnomad OTH exome

AF:

0.00626

GnomAD4 exome

AF:

0.00423

AC:

6096

AN:

1440926

Hom.:

Cov.:

AF XY:

0.00409

AC XY:

2925

AN XY:

715704

show subpopulations

African (AFR)

AF:

0.000721

AC:

AN:

33298

American (AMR)

AF:

0.0169

AC:

748

AN:

44146

Ashkenazi Jewish (ASJ)

AF:

0.00696

AC:

177

AN:

25440

East Asian (EAS)

AF:

0.000908

AC:

AN:

38566

South Asian (SAS)

AF:

0.00102

AC:

AN:

85362

European-Finnish (FIN)

AF:

0.00577

AC:

266

AN:

46130

Middle Eastern (MID)

AF:

0.000527

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00415

AC:

4573

AN:

1102784

Other (OTH)

AF:

0.00308

AC:

183

AN:

59512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

302

604

907

1209

1511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

170

340

510

680

850

<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:

0.00399

AC:

602

AN:

150938

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

271

AN XY:

73792

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

41318

American (AMR)

AF:

0.00962

AC:

145

AN:

15070

Ashkenazi Jewish (ASJ)

AF:

0.00868

AC:

AN:

3456

East Asian (EAS)

AF:

0.00158

AC:

AN:

5064

South Asian (SAS)

AF:

0.000840

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00426

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00467

AC:

315

AN:

67424

Other (OTH)

AF:

0.00531

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00574

Hom.:

Bravo

AF:

0.00464

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

CARD11-related disorder (1)

not provided (1)

not specified (1)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.5

(source)

DANN

Benign

0.26

PhyloP100

0.51

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000099

dbscSNV1_RF

Benign

0.0020

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

Computational scores

Splicing

Publications

Other links and lift over