dbSNP rs10870077: CARD9:c.1077+311G>C (chr9-136369439-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.19

Publications

42 publications found

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 Gene-Disease associations (from GenCC):

deep dermatophytosis
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
predisposition to invasive fungal disease due to CARD9 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

CARD9 links:

ENSG00000289701 (HGNC:):

ENSG00000289701 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5 link	c.1077+311G>C	intron_variant	Intron 7 of 12	ENST00000371732.10	NP_434700.2	Q9H257-1A0A024R8F1
CARD9	NM_052814.4 link	c.1077+311G>C	intron_variant	Intron 7 of 12		NP_434701.1	Q9H257-2
LOC124902309	XR_007061863.1 link	n.*142C>G	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10 link	c.1077+311G>C		intron_variant	Intron 7 of 12	1	NM_052813.5	ENSP00000360797.5		Q9H257-1
ENSG00000289701	ENST00000696169.1 link	n.1077+311G>C		intron_variant	Intron 7 of 12			ENSP00000512460.1

Frequencies

GnomAD3 genomes

AF:

0.381

AC:

57947

AN:

151992

Hom.:

11442

Cov.:

show subpopulations

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.:

AF XY:

0.379

AC XY:

28191

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.293

AC:

12154

AN:

41500

American (AMR)

AF:

0.465

AC:

7105

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.358

AC:

1241

AN:

3468

East Asian (EAS)

AF:

0.310

AC:

1602

AN:

5166

South Asian (SAS)

AF:

0.329

AC:

1585

AN:

4816

European-Finnish (FIN)

AF:

0.411

AC:

4355

AN:

10584

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.423

AC:

28765

AN:

67982

Other (OTH)

AF:

0.361

AC:

764

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1846

3691

5537

7382

9228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.56

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over