NM_052813.5:c.*292T>G

Variant names:

• chr9-136364010-A-C
• rs1135314
• NM_052813.5:c.*292T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052813.5(CARD9):​c.*292T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,146,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: CARD9 NM_052813.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

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.*292T>G		3_prime_UTR	Exon 13 of 13	NP_434700.2
	CARD9	NM_052814.4		c.*115T>G		3_prime_UTR	Exon 13 of 13	NP_434701.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD9	ENST00000371732.10	TSL:1 MANE Select	c.*292T>G		3_prime_UTR	Exon 13 of 13	ENSP00000360797.5
	ENSG00000289701	ENST00000696169.1		n.*1531T>G		non_coding_transcript_exon	Exon 12 of 13	ENSP00000512460.1
	ENSG00000289701	ENST00000696169.1		n.*1531T>G		3_prime_UTR	Exon 12 of 13	ENSP00000512460.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000262 AC: 3 AN: 1146018 Hom.: 0 Cov.: 16 AF XY: 0.00000347 AC XY: 2 AN XY: 576432

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000376 AC: 1 AN: 26624

American (AMR) AF: 0.00 AC: 0 AN: 35406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23600

East Asian (EAS) AF: 0.00 AC: 0 AN: 34650

South Asian (SAS) AF: 0.00 AC: 0 AN: 74120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5246

European-Non Finnish (NFE) AF: 0.00000236 AC: 2 AN: 849218

Other (OTH) AF: 0.00 AC: 0 AN: 49706

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.41
PhyloP100		-0.079
PromoterAI		0.0073	Neutral

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: rs1135314; hg19: chr9-139258462;