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rs117428786

chr7-2906704-G-Achr7-2906704-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_032415.7(CARD11):c.3399C>T(p.Arg1133=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,613,998 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. R1133R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0020 ( 12 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 63 hom. )

Consequence

CARD11
NM_032415.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-2906704-G-A is Benign according to our data. Variant chr7-2906704-G-A is described in ClinVar as [Benign]. Clinvar id is 473935.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-4 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CARD11NM_032415.7 linkuse as main transcriptc.3399C>T p.Arg1133= synonymous_variant 25/25 ENST00000396946.9
CARD11NM_001324281.3 linkuse as main transcriptc.3399C>T p.Arg1133= synonymous_variant 26/26

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CARD11ENST00000396946.9 linkuse as main transcriptc.3399C>T p.Arg1133= synonymous_variant 25/251 NM_032415.7 P1
CARD11ENST00000698637.1 linkuse as main transcriptn.4509C>T non_coding_transcript_exon_variant 24/24
CARD11ENST00000698652.1 linkuse as main transcriptn.2355C>T non_coding_transcript_exon_variant 8/8

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00199
AC:
303
AN:
152242
Hom.:
12
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0546
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00452
AC:
1136
AN:
251208
Hom.:
29
AF XY:
0.00402
AC XY:
546
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0589
Gnomad SAS exome
AF:
0.000915
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00167
AC:
2440
AN:
1461638
Hom.:
63
Cov.:
30
AF XY:
0.00160
AC XY:
1160
AN XY:
727134
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0546
Gnomad4 SAS exome
AF:
0.000800
Gnomad4 FIN exome
AF:
0.0000564
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.00262
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00197
AC:
300
AN:
152360
Hom.:
12
Cov.:
33
AF XY:
0.00220
AC XY:
164
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0542
Gnomad4 SAS
AF:
0.00186
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000257
Hom.:
1
Bravo
AF:
0.00262
Asia WGS
AF:
0.0130
AC:
45
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Severe combined immunodeficiency due to CARD11 deficiency;C4551967:BENTA disease Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.43
Cadd
Benign
0.40
Dann
Benign
0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs117428786; hg19: chr7-2946338; COSMIC: COSV67802179; API