rs768039619

Variant names:

• chr9-136364308-G-A
• rs768039619
• NM_052813.5:c.1605C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-136364308-G-A
• chr9-136364308-G-C
• chr9-136364308-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_052813.5(CARD9):​c.1605C>T​(p.Gly535Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,405,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: CARD9 NM_052813.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10
• Publications: 1 publications found

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

ENSG00000289701 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 9-136364308-G-A is Benign according to our data. Variant chr9-136364308-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1907523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.1 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5	c.1605C>T	p.Gly535Gly	synonymous_variant	Exon 13 of 13	ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4	c.1442-146C>T		intron_variant	Intron 12 of 12		NP_434701.1
LOC124902309	XR_007061863.1	n.84+856G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10	c.1605C>T	p.Gly535Gly	synonymous_variant	Exon 13 of 13	1	NM_052813.5	ENSP00000360797.5
ENSG00000289701	ENST00000696169.1	n.*1233C>T		non_coding_transcript_exon_variant	Exon 12 of 13			ENSP00000512460.1
ENSG00000289701	ENST00000696169.1	n.*1233C>T		3_prime_UTR_variant	Exon 12 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.0000304 AC: 5 AN: 164744 AF XY: 0.0000342

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000764

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000384 AC: 54 AN: 1405494 Hom.: 0 Cov.: 32 AF XY: 0.0000346 AC XY: 24 AN XY: 694172

African (AFR) AF: 0.00 AC: 0 AN: 32030

American (AMR) AF: 0.00 AC: 0 AN: 36538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25244

East Asian (EAS) AF: 0.00 AC: 0 AN: 36622

South Asian (SAS) AF: 0.00 AC: 0 AN: 79870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.0000499 AC: 54 AN: 1083188

Other (OTH) AF: 0.00 AC: 0 AN: 58278

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Predisposition to invasive fungal disease due to CARD9 deficiency Benign:1

Apr 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs768039619; hg19: chr9-139258760;