chr9-136369439-C-G

Position:

• chr9-136369439-C-G

Variant summary

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

The NM_052813.5(CARD9):​c.1077+311G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,110 control chromosomes in the GnomAD database, including 11,461 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 0.38 (11461 hom., cov: 33)
• Consequence: CARD9 NM_052813.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD9	NM_052813.5	c.1077+311G>C		intron_variant		ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4	c.1077+311G>C		intron_variant			NP_434701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10	c.1077+311G>C		intron_variant		1	NM_052813.5	ENSP00000360797	P1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57947 AN: 151992 Hom.: 11442 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.381 AC: 58016 AN: 152110 Hom.: 11461 Cov.: 33 AF XY: 0.379 AC XY: 28191 AN XY: 74356

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.310

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.411

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.361

Alfa AF: 0.414 Hom.: 1663

Bravo AF: 0.379

Asia WGS AF: 0.395 AC: 1374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.32
DANN	Benign	0.56

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: rs10870077; hg19: chr9-139263891; COSMIC: COSV59996740; COSMIC: COSV59996740;