7-2913280-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_032415.7(CARD11):c.3019+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 1,588,244 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CARD11
NM_032415.7 splice_region, intron

Scores

Splicing: ADA: 0.00001580

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.232

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-2913280-C-T is Benign according to our data. Variant chr7-2913280-C-T is described in ClinVar as Benign. ClinVar VariationId is 540985.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00154 (231/150342) while in subpopulation AFR AF = 0.00529 (218/41188). AF 95% confidence interval is 0.00472. There are 0 homozygotes in GnomAd4. There are 107 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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+7G>A		splice_region intron	N/A	NP_115791.3
	CARD11	NM_001324281.3		c.3019+7G>A		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+7G>A	splice_region intron	N/A	ENSP00000380150.4	Q9BXL7
CARD11	ENST00000888804.1		c.3019+7G>A	splice_region intron	N/A	ENSP00000558863.1
CARD11	ENST00000888805.1		c.3019+7G>A	splice_region intron	N/A	ENSP00000558864.1

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

231

AN:

150228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000600

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000298

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000275

AC:

AN:

236492

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.00380

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000373

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000131

AC:

189

AN:

1437902

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

714042

show subpopulations

African (AFR)

AF:

0.00365

AC:

121

AN:

33188

American (AMR)

AF:

0.0000680

AC:

AN:

44104

Ashkenazi Jewish (ASJ)

AF:

0.0000394

AC:

AN:

25402

East Asian (EAS)

AF:

0.0000264

AC:

AN:

37950

South Asian (SAS)

AF:

0.0000471

AC:

AN:

84984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.0000409

AC:

AN:

1101066

Other (OTH)

AF:

0.000236

AC:

AN:

59344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00154

AC:

231

AN:

150342

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

107

AN XY:

73514

show subpopulations

African (AFR)

AF:

0.00529

AC:

218

AN:

41188

American (AMR)

AF:

0.000599

AC:

AN:

15024

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

5008

South Asian (SAS)

AF:

0.000212

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000298

AC:

AN:

67118

Other (OTH)

AF:

0.00

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000641

Hom.:

Bravo

AF:

0.00169

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

-0.81

CADD

Benign

0.026

(source)

DANN

Benign

0.63

PhyloP100

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.012

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