7-2906827-T-C

Position:

chr7-2906827-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032415.7(CARD11):c.3276A>G(p.Arg1092Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,612,394 control chromosomes in the GnomAD database, including 206,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23029 hom., cov: 33)

Exomes 𝑓: 0.50 ( 183751 hom. )

Consequence

CARD11
NM_032415.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.383

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 links:

CARD11 (HGNC:):

CARD11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-2906827-T-C is Benign according to our data. Variant chr7-2906827-T-C is described in ClinVar as [Benign]. Clinvar id is 402477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.383 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD11	NM_032415.7 linkuse as main transcript	c.3276A>G	p.Arg1092Arg	synonymous_variant	25/25	ENST00000396946.9	NP_115791.3	Q9BXL7A0A024R854Q8TES3
CARD11	NM_001324281.3 linkuse as main transcript	c.3276A>G	p.Arg1092Arg	synonymous_variant	26/26		NP_001311210.1	Q9BXL7A0A024R854Q8TES3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CARD11	ENST00000396946.9 linkuse as main transcript	c.3276A>G	p.Arg1092Arg	synonymous_variant	25/25	1	NM_032415.7	ENSP00000380150.4	Q9BXL7
CARD11	ENST00000698637.1 linkuse as main transcript	n.4386A>G		non_coding_transcript_exon_variant	24/24
CARD11	ENST00000698652.1 linkuse as main transcript	n.2232A>G		non_coding_transcript_exon_variant	8/8

Frequencies

GnomAD3 genomes

AF:

0.544

AC:

82663

AN:

151966

Hom.:

22999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.528

Gnomad ASJ

AF:

0.453

Gnomad EAS

AF:

0.638

Gnomad SAS

AF:

0.565

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.536

GnomAD3 exomes

AF:

0.510

AC:

126307

AN:

247676

Hom.:

32723

AF XY:

0.509

AC XY:

68337

AN XY:

134278

show subpopulations

Gnomad AFR exome

AF:

0.661

Gnomad AMR exome

AF:

0.498

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.644

Gnomad SAS exome

AF:

0.550

Gnomad FIN exome

AF:

0.415

Gnomad NFE exome

AF:

0.484

Gnomad OTH exome

AF:

0.472

GnomAD4 exome

AF:

0.499

AC:

729248

AN:

1460310

Hom.:

183751

Cov.:

AF XY:

0.500

AC XY:

363088

AN XY:

726452

show subpopulations

Gnomad4 AFR exome

AF:

0.663

Gnomad4 AMR exome

AF:

0.501

Gnomad4 ASJ exome

AF:

0.457

Gnomad4 EAS exome

AF:

0.604

Gnomad4 SAS exome

AF:

0.545

Gnomad4 FIN exome

AF:

0.414

Gnomad4 NFE exome

AF:

0.492

Gnomad4 OTH exome

AF:

0.505

GnomAD4 genome

AF:

0.544

AC:

82741

AN:

152084

Hom.:

23029

Cov.:

AF XY:

0.542

AC XY:

40306

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.670

Gnomad4 AMR

AF:

0.528

Gnomad4 ASJ

AF:

0.453

Gnomad4 EAS

AF:

0.637

Gnomad4 SAS

AF:

0.566

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.488

Gnomad4 OTH

AF:

0.542

Alfa

AF:

0.503

Hom.:

30606

Bravo

AF:

0.555

Asia WGS

AF:

0.621

AC:

2160

AN:

3478

EpiCase

AF:

0.495

EpiControl

AF:

0.494

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 73% of patients studied by a panel of primary immunodeficiencies. Number of patients: 70. Only high quality variants are reported. -

BENTA disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Immunodeficiency 11b with atopic dermatitis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Severe combined immunodeficiency due to CARD11 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.3

DANN

Benign

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over