Variant rs745730969 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052813.5(CARD9):c.1565G>T(p.Arg522Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CARD9
NM_052813.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09379682).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5 link	c.1565G>T	p.Arg522Leu	missense_variant	Exon 13 of 13	ENST00000371732.10	NP_434700.2	Q9H257-1A0A024R8F1
CARD9	NM_052814.4 link	c.1442-186G>T		intron_variant	Intron 12 of 12		NP_434701.1	Q9H257-2
LOC124902309	XR_007061863.1 link	n.84+896C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CARD9	ENST00000371732.10 link	c.1565G>T	p.Arg522Leu	missense_variant	Exon 13 of 13	1	NM_052813.5	ENSP00000360797.5	Q9H257-1
ENSG00000289701	ENST00000696169.1 link	n.*1193G>T		non_coding_transcript_exon_variant	Exon 12 of 13			ENSP00000512460.1
ENSG00000289701	ENST00000696169.1 link	n.*1193G>T		3_prime_UTR_variant	Exon 12 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1417154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701138

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.033

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.75

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.33

PROVEAN

Benign

0.42

REVEL

Benign

0.16

Sift

Benign

0.32

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.28

MutPred

0.17

Loss of phosphorylation at T525 (P = 0.0573);

MVP

0.14

MPC

0.098

ClinPred

0.10

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.062

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over