rs78443994

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_032415.7(CARD11):c.1975G>A(p.Val659Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,605,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CARD11
NM_032415.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -0.0570

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009144366).

BP6

Variant 7-2923299-C-T is Benign according to our data. Variant chr7-2923299-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 133793.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000598 (91/152176) while in subpopulation AFR AF= 0.00183 (76/41530). AF 95% confidence interval is 0.0015. There are 0 homozygotes in gnomad4. There are 50 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD11	NM_032415.7 link	c.1975G>A	p.Val659Met	missense_variant	Exon 16 of 25	ENST00000396946.9	NP_115791.3	Q9BXL7A0A024R854Q8TES3
CARD11	NM_001324281.3 link	c.1975G>A	p.Val659Met	missense_variant	Exon 17 of 26		NP_001311210.1	Q9BXL7A0A024R854Q8TES3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CARD11	ENST00000396946.9 link	c.1975G>A	p.Val659Met	missense_variant	Exon 16 of 25	1	NM_032415.7	ENSP00000380150.4	Q9BXL7
CARD11	ENST00000355508.3 link	c.388G>A	p.Val130Met	missense_variant	Exon 5 of 7	3		ENSP00000347695.3	H7BY05
CARD11	ENST00000698637.1 link	n.2301G>A		non_coding_transcript_exon_variant	Exon 16 of 24

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000232

AC:

AN:

241368

Hom.:

AF XY:

0.000167

AC XY:

AN XY:

131864

show subpopulations

Gnomad AFR exome

AF:

0.00134

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00222

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000984

Gnomad FIN exome

AF:

0.0000623

Gnomad NFE exome

AF:

0.0000543

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000147

AC:

214

AN:

1453218

Hom.:

Cov.:

AF XY:

0.000122

AC XY:

AN XY:

723188

show subpopulations

Gnomad4 AFR exome

AF:

0.00197

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00280

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000436

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000598

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000228

Hom.:

Bravo

AF:

0.000646

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

Benign:1

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.057

Sift

Benign

0.15

T;T

Sift4G

Benign

0.11

T;.

Polyphen

0.47

P;.

Vest4

0.093

MVP

0.51

MPC

0.47

ClinPred

0.0059

GERP RS

1.6

Varity_R

0.028

gMVP

0.23

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