9-136370636-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_052813.5(CARD9):c.693G>A(p.Thr231Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 1,612,742 control chromosomes in the GnomAD database, including 1,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 141 hom., cov: 34)

Exomes 𝑓: 0.034 ( 991 hom. )

Consequence

CARD9
NM_052813.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.04

Publications

23 publications found

Variant links:

Genes affected

CARD9 (HGNC:16391): (caspase recruitment domain family member 9) The protein encoded by this gene is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated recruitment domain (CARD). CARD is a protein interaction domain known to participate in activation or suppression of CARD containing members of the caspase family, and thus plays an important regulatory role in cell apoptosis. This protein was identified by its selective association with the CARD domain of BCL10, a postive regulator of apoptosis and NF-kappaB activation, and is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-kappaB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined. [provided by RefSeq, Jul 2008]

CARD9 Gene-Disease associations (from GenCC):

deep dermatophytosis
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
predisposition to invasive fungal disease due to CARD9 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

CARD9 links:

ENSG00000289701 (HGNC:):

ENSG00000289701 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 9-136370636-C-T is Benign according to our data. Variant chr9-136370636-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 365848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5 link	c.693G>A	p.Thr231Thr	synonymous_variant	Exon 5 of 13	ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4 link	c.693G>A	p.Thr231Thr	synonymous_variant	Exon 5 of 13		NP_434701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10 link	c.693G>A	p.Thr231Thr	synonymous_variant	Exon 5 of 13	1	NM_052813.5	ENSP00000360797.5
ENSG00000289701	ENST00000696169.1 link	n.693G>A		non_coding_transcript_exon_variant	Exon 5 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6055

AN:

152232

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0163

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.0973

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0454

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0336

Gnomad OTH

AF:

0.0306

GnomAD2 exomes

AF:

0.0386

AC:

9617

AN:

249382

AF XY:

0.0383

show subpopulations

Gnomad AFR exome

AF:

0.0523

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.0439

Gnomad NFE exome

AF:

0.0337

Gnomad OTH exome

AF:

0.0341

GnomAD4 exome

AF:

0.0336

AC:

49133

AN:

1460392

Hom.:

991

Cov.:

AF XY:

0.0339

AC XY:

24600

AN XY:

726488

show subpopulations

African (AFR)

AF:

0.0492

AC:

1646

AN:

33474

American (AMR)

AF:

0.0124

AC:

556

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

790

AN:

26122

East Asian (EAS)

AF:

0.0832

AC:

3303

AN:

39688

South Asian (SAS)

AF:

0.0399

AC:

3441

AN:

86256

European-Finnish (FIN)

AF:

0.0455

AC:

2373

AN:

52116

Middle Eastern (MID)

AF:

0.00936

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0313

AC:

34757

AN:

1111880

Other (OTH)

AF:

0.0367

AC:

2213

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3913

7826

11739

15652

19565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1310

2620

3930

5240

6550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0398

AC:

6065

AN:

152350

Hom.:

141

Cov.:

AF XY:

0.0400

AC XY:

2980

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.0501

AC:

2085

AN:

41586

American (AMR)

AF:

0.0162

AC:

248

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3468

East Asian (EAS)

AF:

0.0969

AC:

502

AN:

5178

South Asian (SAS)

AF:

0.0526

AC:

254

AN:

4830

European-Finnish (FIN)

AF:

0.0454

AC:

483

AN:

10632

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0336

AC:

2289

AN:

68024

Other (OTH)

AF:

0.0322

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

311

622

932

1243

1554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0370

Hom.:

Bravo

AF:

0.0370

Asia WGS

AF:

0.0950

AC:

331

AN:

3478

EpiCase

AF:

0.0302

EpiControl

AF:

0.0290

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Predisposition to invasive fungal disease due to CARD9 deficiency

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.85

(source)

DANN

Benign

0.87

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over