7-2937133-G-A

Position:

chr7-2937133-G-A

Variant summary

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

The NM_032415.7(CARD11):c.1245C>T(p.Asp415=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,614,084 control chromosomes in the GnomAD database, including 27,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1956 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25733 hom. )

Consequence

CARD11
NM_032415.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.431

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 7-2937133-G-A is Benign according to our data. Variant chr7-2937133-G-A is described in ClinVar as [Benign]. Clinvar id is 402481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.431 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD11	NM_032415.7 linkuse as main transcript	c.1245C>T	p.Asp415=	synonymous_variant	9/25	ENST00000396946.9
CARD11	NM_001324281.3 linkuse as main transcript	c.1245C>T	p.Asp415=	synonymous_variant	10/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CARD11	ENST00000396946.9 linkuse as main transcript	c.1245C>T	p.Asp415=	synonymous_variant	9/25	1	NM_032415.7	P1
CARD11	ENST00000698637.1 linkuse as main transcript	n.1571C>T		non_coding_transcript_exon_variant	9/24
CARD11	ENST00000698654.1 linkuse as main transcript	n.1504C>T		non_coding_transcript_exon_variant	9/10
CARD11	ENST00000698662.1 linkuse as main transcript	n.1445C>T		non_coding_transcript_exon_variant	9/10

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22425

AN:

152130

Hom.:

1954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0728

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.00769

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.164

AC:

41111

AN:

251382

Hom.:

4071

AF XY:

0.162

AC XY:

22038

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0686

Gnomad AMR exome

AF:

0.207

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.00414

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.182

GnomAD4 exome

AF:

0.181

AC:

264066

AN:

1461836

Hom.:

25733

Cov.:

AF XY:

0.179

AC XY:

130204

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0685

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.00290

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.147

AC:

22430

AN:

152248

Hom.:

1956

Cov.:

AF XY:

0.147

AC XY:

10925

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0727

Gnomad4 AMR

AF:

0.156

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.00751

Gnomad4 SAS

AF:

0.0968

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.139

Alfa

AF:

0.122

Hom.:

356

Bravo

AF:

0.139

Asia WGS

AF:

0.0640

AC:

224

AN:

3478

EpiCase

AF:

0.182

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -
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: MAF -

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

Invitae

Jan 31, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.3

DANN

Benign

0.78

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