rs1135314

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052813.5(CARD9):c.*292T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,296,282 control chromosomes in the GnomAD database, including 69,305 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7620 hom., cov: 35)

Exomes 𝑓: 0.32 ( 61685 hom. )

Consequence

CARD9
NM_052813.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0790

Variant links:

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 links:

ENSG00000289701 (HGNC:):

ENSG00000289701 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-136364010-A-G is Benign according to our data. Variant chr9-136364010-A-G is described in ClinVar as [Benign]. Clinvar id is 365828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5 link	c.*292T>C	3_prime_UTR_variant	Exon 13 of 13	ENST00000371732.10	NP_434700.2	Q9H257-1A0A024R8F1
CARD9	NM_052814.4 link	c.*115T>C	3_prime_UTR_variant	Exon 13 of 13		NP_434701.1	Q9H257-2
LOC124902309	XR_007061863.1 link	n.84+558A>G	intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CARD9	ENST00000371732 link	c.*292T>C	3_prime_UTR_variant	Exon 13 of 13	1	NM_052813.5	ENSP00000360797.5	Q9H257-1
ENSG00000289701	ENST00000696169.1 link	n.*1531T>C	non_coding_transcript_exon_variant	Exon 12 of 13			ENSP00000512460.1
ENSG00000289701	ENST00000696169.1 link	n.*1531T>C	3_prime_UTR_variant	Exon 12 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46890

AN:

152100

Hom.:

7606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.256

Gnomad AMI

AF:

0.417

Gnomad AMR

AF:

0.419

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.0554

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.332

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.319

AC:

47626

AN:

149294

Hom.:

8577

AF XY:

0.309

AC XY:

24749

AN XY:

80102

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.0436

Gnomad SAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.322

AC:

367936

AN:

1144066

Hom.:

61685

Cov.:

AF XY:

0.318

AC XY:

183053

AN XY:

575504

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.458

Gnomad4 ASJ exome

AF:

0.423

Gnomad4 EAS exome

AF:

0.0928

Gnomad4 SAS exome

AF:

0.239

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.332

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.308

AC:

46942

AN:

152216

Hom.:

7620

Cov.:

AF XY:

0.307

AC XY:

22838

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.256

Gnomad4 AMR

AF:

0.420

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.0554

Gnomad4 SAS

AF:

0.225

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.332

Gnomad4 OTH

AF:

0.337

Alfa

AF:

0.341

Hom.:

3375

Bravo

AF:

0.313

Asia WGS

AF:

0.188

AC:

654

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 75% of patients studied by a panel of primary immunodeficiencies. Number of patients: 66. Only high quality variants are reported. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Predisposition to invasive fungal disease due to CARD9 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.7

DANN

Benign

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over