rs4078098

chr9-136372841-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 129 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD9	NM_052813.5	c.-17+691G>A		intron_variant		ENST00000371732.10
CARD9	NM_052814.4	c.-17+691G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD9	ENST00000371732.10	c.-17+691G>A		intron_variant		1	NM_052813.5	P1

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

Gnomad4 AFR AF: 0.00839

Gnomad4 AMR AF: 0.0427

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.0241

Gnomad4 SAS AF: 0.0410

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.0427

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0396 Hom.: 25

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4078098; hg19: chr9-139267293;