7-2923119-G-A

Position:

chr7-2923119-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032415.7(CARD11):c.2142+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,606,740 control chromosomes in the GnomAD database, including 440,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 32710 hom., cov: 34)

Exomes 𝑓: 0.74 ( 407908 hom. )

Consequence

CARD11
NM_032415.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.293

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-2923119-G-A is Benign according to our data. Variant chr7-2923119-G-A is described in ClinVar as [Benign]. Clinvar id is 402479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.766 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.2142+13C>T		intron_variant		ENST00000396946.9	NP_115791.3	Q9BXL7A0A024R854Q8TES3
CARD11	NM_001324281.3 linkuse as main transcript	c.2142+13C>T		intron_variant			NP_001311210.1	Q9BXL7A0A024R854Q8TES3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
CARD11	ENST00000396946.9 linkuse as main transcript	c.2142+13C>T	intron_variant	1	NM_032415.7	ENSP00000380150.4	Q9BXL7
CARD11	ENST00000355508.3 linkuse as main transcript	c.555+13C>T	intron_variant	3		ENSP00000347695.3	H7BY05
CARD11	ENST00000698637.1 linkuse as main transcript	n.2468+13C>T	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95577

AN:

152080

Hom.:

32712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.651

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.820

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.642

GnomAD3 exomes

AF:

0.676

AC:

164061

AN:

242524

Hom.:

57880

AF XY:

0.683

AC XY:

90314

AN XY:

132242

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.634

Gnomad ASJ exome

AF:

0.731

Gnomad EAS exome

AF:

0.382

Gnomad SAS exome

AF:

0.620

Gnomad FIN exome

AF:

0.815

Gnomad NFE exome

AF:

0.770

Gnomad OTH exome

AF:

0.717

GnomAD4 exome

AF:

0.742

AC:

1078948

AN:

1454542

Hom.:

407908

Cov.:

AF XY:

0.740

AC XY:

535119

AN XY:

723610

show subpopulations

Gnomad4 AFR exome

AF:

0.341

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.725

Gnomad4 EAS exome

AF:

0.412

Gnomad4 SAS exome

AF:

0.625

Gnomad4 FIN exome

AF:

0.815

Gnomad4 NFE exome

AF:

0.778

Gnomad4 OTH exome

AF:

0.707

GnomAD4 genome

AF:

0.628

AC:

95598

AN:

152198

Hom.:

32710

Cov.:

AF XY:

0.627

AC XY:

46637

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.357

Gnomad4 AMR

AF:

0.650

Gnomad4 ASJ

AF:

0.729

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.602

Gnomad4 FIN

AF:

0.820

Gnomad4 NFE

AF:

0.771

Gnomad4 OTH

AF:

0.638

Alfa

AF:

0.719

Hom.:

9922

Bravo

AF:

0.603

Asia WGS

AF:

0.501

AC:

1741

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

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 64% of patients studied by a panel of primary immunodeficiencies. Number of patients: 61. 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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 04, 2019

- -

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

-0.84

CADD

Benign

1.4

DANN

Benign

0.63

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