rs10781499

Positions:

chr9-136371953-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000371732.10(CARD9):c.126C>T(p.Pro42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,609,980 control chromosomes in the GnomAD database, including 140,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11482 hom., cov: 34)

Exomes 𝑓: 0.42 ( 129058 hom. )

Consequence

CARD9
ENST00000371732.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 9-136371953-G-A is Benign according to our data. Variant chr9-136371953-G-A is described in ClinVar as [Benign]. Clinvar id is 365857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-136371953-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD9	NM_052813.5 linkuse as main transcript	c.126C>T	p.Pro42=	synonymous_variant	2/13	ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4 linkuse as main transcript	c.126C>T	p.Pro42=	synonymous_variant	2/13		NP_434701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10 linkuse as main transcript	c.126C>T	p.Pro42=	synonymous_variant	2/13	1	NM_052813.5	ENSP00000360797	P1	Q9H257-1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57880

AN:

152020

Hom.:

11464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.288

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.329

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.407

AC:

102015

AN:

250490

Hom.:

21600

AF XY:

0.399

AC XY:

54106

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.283

Gnomad AMR exome

AF:

0.537

Gnomad ASJ exome

AF:

0.358

Gnomad EAS exome

AF:

0.297

Gnomad SAS exome

AF:

0.327

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.427

Gnomad OTH exome

AF:

0.411

GnomAD4 exome

AF:

0.417

AC:

607724

AN:

1457842

Hom.:

129058

Cov.:

AF XY:

0.413

AC XY:

299109

AN XY:

724554

show subpopulations

Gnomad4 AFR exome

AF:

0.278

Gnomad4 AMR exome

AF:

0.535

Gnomad4 ASJ exome

AF:

0.355

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.417

Gnomad4 NFE exome

AF:

0.431

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.381

AC:

57944

AN:

152138

Hom.:

11482

Cov.:

AF XY:

0.379

AC XY:

28175

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.288

Gnomad4 AMR

AF:

0.475

Gnomad4 ASJ

AF:

0.357

Gnomad4 EAS

AF:

0.309

Gnomad4 SAS

AF:

0.329

Gnomad4 FIN

AF:

0.411

Gnomad4 NFE

AF:

0.423

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.407

Hom.:

21366

Bravo

AF:

0.379

Asia WGS

AF:

0.385

AC:

1338

AN:

3478

EpiCase

AF:

0.393

EpiControl

AF:

0.408

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Predisposition to invasive fungal disease due to CARD9 deficiency

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:2

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 76% of patients studied by a panel of primary immunodeficiencies. Number of patients: 67. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.2

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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