NM_052813.5:c.297G>A

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.297G>A(p.Pro99Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,602,174 control chromosomes in the GnomAD database, including 838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 82 hom., cov: 34)

Exomes 𝑓: 0.020 ( 756 hom. )

Consequence

CARD9
NM_052813.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.818

Publications

7 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=-0.85).

BP6

Variant 9-136371349-C-T is Benign according to our data. Variant chr9-136371349-C-T is described in ClinVar as Benign. ClinVar VariationId is 365853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.818 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5 link	c.297G>A	p.Pro99Pro	synonymous_variant	Exon 3 of 13	ENST00000371732.10	NP_434700.2	Q9H257-1A0A024R8F1
CARD9	NM_052814.4 link	c.297G>A	p.Pro99Pro	synonymous_variant	Exon 3 of 13		NP_434701.1	Q9H257-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10 link	c.297G>A	p.Pro99Pro	synonymous_variant	Exon 3 of 13	1	NM_052813.5	ENSP00000360797.5		Q9H257-1
ENSG00000289701	ENST00000696169.1 link	n.297G>A		non_coding_transcript_exon_variant	Exon 3 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2921

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00557

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.0869

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0130

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0186

GnomAD2 exomes

AF:

0.0326

AC:

7451

AN:

228396

AF XY:

0.0269

show subpopulations

Gnomad AFR exome

AF:

0.00533

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.000117

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0200

AC:

29002

AN:

1449844

Hom.:

756

Cov.:

AF XY:

0.0190

AC XY:

13712

AN XY:

720220

show subpopulations

African (AFR)

AF:

0.00420

AC:

140

AN:

33346

American (AMR)

AF:

0.148

AC:

6404

AN:

43152

Ashkenazi Jewish (ASJ)

AF:

0.00398

AC:

103

AN:

25848

East Asian (EAS)

AF:

0.000688

AC:

AN:

39240

South Asian (SAS)

AF:

0.00391

AC:

331

AN:

84548

European-Finnish (FIN)

AF:

0.0178

AC:

909

AN:

51058

Middle Eastern (MID)

AF:

0.00452

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0180

AC:

19980

AN:

1106976

Other (OTH)

AF:

0.0181

AC:

1082

AN:

59920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

1938

3876

5813

7751

9689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.0193

AC:

2933

AN:

152330

Hom.:

Cov.:

AF XY:

0.0193

AC XY:

1436

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00556

AC:

231

AN:

41574

American (AMR)

AF:

0.0876

AC:

1340

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.00207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0130

AC:

138

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0169

AC:

1147

AN:

68022

Other (OTH)

AF:

0.0184

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

158

316

475

633

791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0167

Hom.:

Bravo

AF:

0.0254

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Predisposition to invasive fungal disease due to CARD9 deficiency

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 08, 2018

Illumina Laboratory Services, Illumina

Significance: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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 25% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: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

-0.85

CADD

Benign

0.69

(source)

DANN

Benign

0.90

PhyloP100

-0.82

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