NM_052813.5:c.-17+691G>A

Variant names:

• chr9-136372841-C-T
• rs4078098
• NM_052813.5:c.-17+691G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_052813.5(CARD9):​c.-17+691G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 152,334 control chromosomes in the GnomAD database, including 131 homozygotes. 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: 𝑓 0.033 (131 hom., cov: 33)
• Consequence: CARD9 NM_052813.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0329 (5009/152334) while in subpopulation NFE AF = 0.0427 (2907/68028). AF 95% confidence interval is 0.0414. There are 131 homozygotes in GnomAd4. There are 2545 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 131 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5	c.-17+691G>A		intron_variant	Intron 1 of 12	ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4	c.-17+691G>A		intron_variant	Intron 1 of 12		NP_434701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10	c.-17+691G>A		intron_variant	Intron 1 of 12	1	NM_052813.5	ENSP00000360797.5
ENSG00000289701	ENST00000696169.1	n.-17+691G>A		intron_variant	Intron 1 of 12			ENSP00000512460.1

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5001 AN: 152216 Hom.: 129 Cov.: 33

Gnomad AFR AF: 0.00842

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.0243

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0427

Gnomad OTH AF: 0.0373

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0329 AC: 5009 AN: 152334 Hom.: 131 Cov.: 33 AF XY: 0.0342 AC XY: 2545 AN XY: 74490

African (AFR) AF: 0.00839 AC: 349 AN: 41582

American (AMR) AF: 0.0427 AC: 653 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3470

East Asian (EAS) AF: 0.0241 AC: 125 AN: 5180

South Asian (SAS) AF: 0.0410 AC: 198 AN: 4828

European-Finnish (FIN) AF: 0.0374 AC: 397 AN: 10622

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0427 AC: 2907 AN: 68028

Other (OTH) AF: 0.0402 AC: 85 AN: 2112

Alfa AF: 0.0321 Hom.: 47

Bravo AF: 0.0294

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.1
DANN	Benign	0.72
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs4078098; hg19: chr9-139267293;