rs10781496

Variant names:

• chr9-136366634-A-C
• rs10781496
• NM_052813.5:c.1357+166T>G

Your query was ambiguous. Multiple possible variants found:

• chr9-136366634-A-C
• chr9-136366634-A-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.1357+166T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 586,418 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: 33)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: CARD9 NM_052813.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• 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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5	c.1357+166T>G		intron_variant	Intron 10 of 12	ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4	c.1357+166T>G		intron_variant	Intron 10 of 12		NP_434701.1
LOC124902309	XR_007061863.1	n.85-990A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10	c.1357+166T>G		intron_variant	Intron 10 of 12	1	NM_052813.5	ENSP00000360797.5
ENSG00000289701	ENST00000696169.1	n.*404+166T>G		intron_variant	Intron 10 of 12			ENSP00000512460.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000171 AC: 1 AN: 586418 Hom.: 0 Cov.: 7 AF XY: 0.00000319 AC XY: 1 AN XY: 313366

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

African (AFR) AF: 0.00 AC: 0 AN: 16276

American (AMR) AF: 0.0000288 AC: 1 AN: 34702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16646

East Asian (EAS) AF: 0.00 AC: 0 AN: 34770

South Asian (SAS) AF: 0.00 AC: 0 AN: 58548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2330

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 355008

Other (OTH) AF: 0.00 AC: 0 AN: 31140

⚠️ 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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.75
PhyloP100		-0.67

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: rs10781496; hg19: chr9-139261086;