7-2930055-T-G

Position:

chr7-2930055-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_032415.7(CARD11):c.1590A>C(p.Glu530Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,613,792 control chromosomes in the GnomAD database, including 280 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 159 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 121 hom. )

Consequence

CARD11
NM_032415.7 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: -1.63

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 -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CARD11. . Gene score misZ 3.5439 (greater than the threshold 3.09). Trascript score misZ 3.7177 (greater than threshold 3.09). GenCC has associacion of gene with BENTA disease, immunodeficiency 11b with atopic dermatitis, severe combined immunodeficiency due to CARD11 deficiency.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018115938).

BP6

Variant 7-2930055-T-G is Benign according to our data. Variant chr7-2930055-T-G is described in ClinVar as [Benign]. Clinvar id is 133784.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0824 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.1590A>C	p.Glu530Asp	missense_variant	12/25	ENST00000396946.9	NP_115791.3
CARD11	NM_001324281.3 linkuse as main transcript	c.1590A>C	p.Glu530Asp	missense_variant	13/26		NP_001311210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CARD11	ENST00000396946.9 linkuse as main transcript	c.1590A>C	p.Glu530Asp	missense_variant	12/25	1	NM_032415.7	ENSP00000380150	P1
CARD11	ENST00000355508.3 linkuse as main transcript	c.6A>C	p.Glu2Asp	missense_variant	1/7	3		ENSP00000347695
CARD11	ENST00000698637.1 linkuse as main transcript	n.1916A>C		non_coding_transcript_exon_variant	12/24

Frequencies

GnomAD3 genomes

AF:

0.0243

AC:

3698

AN:

152090

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0847

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00805

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00651

AC:

1636

AN:

251178

Hom.:

AF XY:

0.00474

AC XY:

644

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.0884

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.000795

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.00310

GnomAD4 exome

AF:

0.00249

AC:

3645

AN:

1461582

Hom.:

121

Cov.:

AF XY:

0.00219

AC XY:

1589

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.0855

Gnomad4 AMR exome

AF:

0.00452

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000197

Gnomad4 OTH exome

AF:

0.00505

GnomAD4 genome

AF:

0.0244

AC:

3708

AN:

152210

Hom.:

159

Cov.:

AF XY:

0.0230

AC XY:

1714

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0847

Gnomad4 AMR

AF:

0.00804

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.00409

Hom.:

Bravo

AF:

0.0280

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0903

AC:

398

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00777

AC:

943

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000237

ClinVar

Significance: 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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.052

DANN

Benign

0.27

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.62

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.6

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.011

Sift

Benign

0.89

T;T

Sift4G

Benign

0.92

T;.

Polyphen

0.0

B;.

Vest4

0.089

MutPred

0.092

Gain of helix (P = 0.0696);.;

MVP

0.28

MPC

0.40

ClinPred

0.0040

GERP RS

-5.4

Varity_R

0.023

gMVP

0.14

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