rs754404646

chr9-136370283-TGC-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_052813.5(CARD9):c.951+9_951+10del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,598,152 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (9 hom., cov: 34)
  • Exomes 𝑓: 0.00066 (8 hom.)
• Consequence: CARD9 NM_052813.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.110

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 9-136370283-TGC-T is Benign according to our data. Variant chr9-136370283-TGC-T is described in ClinVar as [Benign]. Clinvar id is 535818.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00626 (954/152336) while in subpopulation AFR AF= 0.0213 (885/41584). AF 95% confidence interval is 0.0201. There are 9 homozygotes in gnomad4. There are 440 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD9	NM_052813.5	c.951+9_951+10del		intron_variant		ENST00000371732.10
CARD9	NM_052814.4	c.951+9_951+10del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD9	ENST00000371732.10	c.951+9_951+10del		intron_variant		1	NM_052813.5	P1

Frequencies

GnomAD3 genomes AF: 0.00625 AC: 952 AN: 152218 Hom.: 9 Cov.: 34

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00479

GnomAD4 exome AF: 0.000665 AC: 961 AN: 1445816 Hom.: 8 AF XY: 0.000521 AC XY: 375 AN XY: 719296

Gnomad4 AFR exome AF: 0.0225

Gnomad4 AMR exome AF: 0.00197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000587

Gnomad4 FIN exome AF: 0.0000233

Gnomad4 NFE exome AF: 0.0000270

Gnomad4 OTH exome AF: 0.00145

GnomAD4 genome AF: 0.00626 AC: 954 AN: 152336 Hom.: 9 Cov.: 34 AF XY: 0.00591 AC XY: 440 AN XY: 74498

Gnomad4 AFR AF: 0.0213

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Predisposition to invasive fungal disease due to CARD9 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs754404646; hg19: chr9-139264735;