chr9-136364308-G-A

Variant names:

• chr9-136364308-G-A
• rs768039619
• NM_052813.5:c.1605C>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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

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 VariationId is 1907523.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052813.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD9	NM_052813.5	MANE Select	c.1605C>T	p.Gly535Gly	synonymous	Exon 13 of 13	NP_434700.2
	CARD9	NM_052814.4		c.1442-146C>T		intron	N/A	NP_434701.1	Q9H257-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD9	ENST00000371732.10	TSL:1 MANE Select	c.1605C>T	p.Gly535Gly	synonymous	Exon 13 of 13	ENSP00000360797.5	Q9H257-1
	ENSG00000289701	ENST00000696169.1		n.*1233C>T		non_coding_transcript_exon	Exon 12 of 13	ENSP00000512460.1
	ENSG00000289701	ENST00000696169.1		n.*1233C>T		3_prime_UTR	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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Predisposition to invasive fungal disease due to CARD9 deficiency (1)

Computational scores

Source: dbNSFP v4.9

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;