7-2945952-C-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_032415.7(CARD11):ā€‹c.225G>Cā€‹(p.Arg75Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,613,940 control chromosomes in the GnomAD database, including 1,292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…).

Frequency

Genomes: š‘“ 0.056 ( 616 hom., cov: 32)
Exomes š‘“: 0.016 ( 676 hom. )

Consequence

CARD11
NM_032415.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.32
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-AS1 (HGNC:40766): (CARD11 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 7-2945952-C-G is Benign according to our data. Variant chr7-2945952-C-G is described in ClinVar as [Benign]. Clinvar id is 473930.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.32 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CARD11NM_032415.7 linkc.225G>C p.Arg75Arg synonymous_variant 4/25 ENST00000396946.9 NP_115791.3 Q9BXL7A0A024R854Q8TES3
CARD11NM_001324281.3 linkc.225G>C p.Arg75Arg synonymous_variant 5/26 NP_001311210.1 Q9BXL7A0A024R854Q8TES3
CARD11-AS1NR_187443.1 linkn.475-645C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CARD11ENST00000396946.9 linkc.225G>C p.Arg75Arg synonymous_variant 4/251 NM_032415.7 ENSP00000380150.4 Q9BXL7

Frequencies

GnomAD3 genomes
AF:
0.0556
AC:
8463
AN:
152094
Hom.:
612
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.166
Gnomad AMI
AF:
0.00439
Gnomad AMR
AF:
0.0271
Gnomad ASJ
AF:
0.0150
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.0144
Gnomad MID
AF:
0.0443
Gnomad NFE
AF:
0.0128
Gnomad OTH
AF:
0.0421
GnomAD3 exomes
AF:
0.0212
AC:
5322
AN:
251296
Hom.:
278
AF XY:
0.0179
AC XY:
2437
AN XY:
135808
show subpopulations
Gnomad AFR exome
AF:
0.173
Gnomad AMR exome
AF:
0.0133
Gnomad ASJ exome
AF:
0.0133
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00137
Gnomad FIN exome
AF:
0.0134
Gnomad NFE exome
AF:
0.0131
Gnomad OTH exome
AF:
0.0163
GnomAD4 exome
AF:
0.0156
AC:
22850
AN:
1461728
Hom.:
676
Cov.:
32
AF XY:
0.0146
AC XY:
10625
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.177
Gnomad4 AMR exome
AF:
0.0152
Gnomad4 ASJ exome
AF:
0.0171
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00124
Gnomad4 FIN exome
AF:
0.0140
Gnomad4 NFE exome
AF:
0.0121
Gnomad4 OTH exome
AF:
0.0232
GnomAD4 genome
AF:
0.0558
AC:
8487
AN:
152212
Hom.:
616
Cov.:
32
AF XY:
0.0549
AC XY:
4084
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.166
Gnomad4 AMR
AF:
0.0271
Gnomad4 ASJ
AF:
0.0150
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.0144
Gnomad4 NFE
AF:
0.0128
Gnomad4 OTH
AF:
0.0417
Alfa
AF:
0.0234
Hom.:
46
Bravo
AF:
0.0618
Asia WGS
AF:
0.0140
AC:
49
AN:
3478
EpiCase
AF:
0.0131
EpiControl
AF:
0.0110

ClinVar

Significance: Benign
Submissions summary: Benign:2
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 testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
CARD11-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesApr 02, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
2.9
DANN
Benign
0.60

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: rs10229368; hg19: chr7-2985586; COSMIC: COSV62717184; COSMIC: COSV62717184; API