9-136365192-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_052813.5(CARD9):c.1383G>A(p.Pro461Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00514 in 1,610,312 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 10 hom., cov: 33)

Exomes 𝑓: 0.0051 ( 54 hom. )

Consequence

CARD9
NM_052813.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.73

Publications

3 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=-0.84).

BP6

Variant 9-136365192-C-T is Benign according to our data. Variant chr9-136365192-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 365833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.73 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00589 (897/152176) while in subpopulation NFE AF = 0.00612 (416/67984). AF 95% confidence interval is 0.00563. There are 10 homozygotes in GnomAd4. There are 533 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5 link	c.1383G>A	p.Pro461Pro	synonymous_variant	Exon 11 of 13	ENST00000371732.10	NP_434700.2	Q9H257-1A0A024R8F1
CARD9	NM_052814.4 link	c.1383G>A	p.Pro461Pro	synonymous_variant	Exon 11 of 13		NP_434701.1	Q9H257-2
LOC124902309	XR_007061863.1 link	n.84+1740C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CARD9	ENST00000371732.10 link	c.1383G>A	p.Pro461Pro	synonymous_variant	Exon 11 of 13	1	NM_052813.5	ENSP00000360797.5	Q9H257-1
ENSG00000289701	ENST00000696169.1 link	n.*430G>A		non_coding_transcript_exon_variant	Exon 11 of 13			ENSP00000512460.1
ENSG00000289701	ENST00000696169.1 link	n.*430G>A		3_prime_UTR_variant	Exon 11 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes

AF:

0.00590

AC:

897

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0402

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00612

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00593

AC:

1455

AN:

245460

AF XY:

0.00610

show subpopulations

Gnomad AFR exome

AF:

0.000752

Gnomad AMR exome

AF:

0.000755

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.000328

Gnomad FIN exome

AF:

0.0401

Gnomad NFE exome

AF:

0.00566

Gnomad OTH exome

AF:

0.00546

GnomAD4 exome

AF:

0.00507

AC:

7387

AN:

1458136

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

3609

AN XY:

725570

show subpopulations

African (AFR)

AF:

0.000508

AC:

AN:

33478

American (AMR)

AF:

0.000626

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26122

East Asian (EAS)

AF:

0.000327

AC:

AN:

39698

South Asian (SAS)

AF:

0.000197

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.0353

AC:

1766

AN:

49998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00480

AC:

5333

AN:

1111826

Other (OTH)

AF:

0.00343

AC:

207

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

376

752

1127

1503

1879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

392

588

784

980

<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:

0.00589

AC:

897

AN:

152176

Hom.:

Cov.:

AF XY:

0.00716

AC XY:

533

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.000819

AC:

AN:

41512

American (AMR)

AF:

0.000850

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0402

AC:

426

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00612

AC:

416

AN:

67984

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

142

189

236

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00517

Hom.:

Bravo

AF:

0.00244

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00360

EpiControl

AF:

0.00374

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CARD9: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.5

(source)

DANN

Benign

0.65

PhyloP100

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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