rs10781496

Positions:

• chr9-136366634-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052813.5(CARD9):​c.1357+166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 737,666 control chromosomes in the GnomAD database, including 67,295 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 0.39 (12121 hom., cov: 33)
  • Exomes 𝑓: 0.43 (55174 hom.)
• Consequence: CARD9 NM_052813.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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]

ENSG00000289701 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10	c.1357+166T>C		intron_variant		1	NM_052813.5	ENSP00000360797.5
ENSG00000289701	ENST00000696169.1	n.*404+166T>C		intron_variant				ENSP00000512460.1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59464 AN: 151984 Hom.: 12100 Cov.: 33

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.429 AC: 251446 AN: 585564 Hom.: 55174 Cov.: 7 AF XY: 0.425 AC XY: 132917 AN XY: 312906

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.533

Gnomad4 ASJ exome AF: 0.366

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.371

Gnomad4 FIN exome AF: 0.467

Gnomad4 NFE exome AF: 0.446

Gnomad4 OTH exome AF: 0.419

GnomAD4 genome AF: 0.391 AC: 59529 AN: 152102 Hom.: 12121 Cov.: 33 AF XY: 0.391 AC XY: 29097 AN XY: 74350

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.376

Alfa AF: 0.424 Hom.: 11932

Bravo AF: 0.384

Asia WGS AF: 0.417 AC: 1453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.78

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: rs10781496; hg19: chr9-139261086; COSMIC: COSV59996723; COSMIC: COSV59996723;