chr9-136364056-G-A

Variant names:

• chr9-136364056-G-A
• rs570507065
• ENST00000696169.1:n.*1485C>T

Variant summary

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

The ENST00000696169.1(ENSG00000289701):​n.*1485C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,381,112 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: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ENSG00000289701 ENST00000696169.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 0 publications found

Genes affected

ENSG00000289701 (HGNC:):

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

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=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5	c.*246C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4	c.*69C>T		3_prime_UTR_variant	Exon 13 of 13		NP_434701.1
LOC124902309	XR_007061863.1	n.84+604G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000289701	ENST00000696169.1	n.*1485C>T		non_coding_transcript_exon_variant	Exon 12 of 13			ENSP00000512460.1
CARD9	ENST00000371732.10	c.*246C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_052813.5	ENSP00000360797.5
ENSG00000289701	ENST00000696169.1	n.*1485C>T		3_prime_UTR_variant	Exon 12 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000652 AC: 1 AN: 153352 AF XY: 0.0000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1381112 Hom.: 0 Cov.: 28 AF XY: 0.00000147 AC XY: 1 AN XY: 682222

African (AFR) AF: 0.00 AC: 0 AN: 31230

American (AMR) AF: 0.0000280 AC: 1 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25088

East Asian (EAS) AF: 0.00 AC: 0 AN: 35788

South Asian (SAS) AF: 0.00 AC: 0 AN: 78864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1063358

Other (OTH) AF: 0.00 AC: 0 AN: 57446

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.5
DANN	Benign	0.78
PhyloP100		-1.0
PromoterAI		-0.012	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: rs570507065; hg19: chr9-139258508;