rs10781496

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000371732.10(CARD9):​c.1357+166T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 737,666 control chromosomes in the GnomAD database, including 67,295 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 0.39 ( 12121 hom., cov: 33)
Exomes 𝑓: 0.43 ( 55174 hom. )

Consequence

CARD9
ENST00000371732.10 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.670
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CARD9NM_052813.5 linkuse as main transcriptc.1357+166T>C intron_variant ENST00000371732.10 NP_434700.2
LOC124902309XR_007061863.1 linkuse as main transcriptn.85-990A>G intron_variant, non_coding_transcript_variant
CARD9NM_052814.4 linkuse as main transcriptc.1357+166T>C intron_variant NP_434701.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CARD9ENST00000371732.10 linkuse as main transcriptc.1357+166T>C intron_variant 1 NM_052813.5 ENSP00000360797 P1Q9H257-1

Frequencies

GnomAD3 genomes
AF:
0.391
AC:
59464
AN:
151984
Hom.:
12100
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.281
Gnomad AMI
AF:
0.418
Gnomad AMR
AF:
0.468
Gnomad ASJ
AF:
0.368
Gnomad EAS
AF:
0.321
Gnomad SAS
AF:
0.384
Gnomad FIN
AF:
0.458
Gnomad MID
AF:
0.228
Gnomad NFE
AF:
0.439
Gnomad OTH
AF:
0.373
GnomAD4 exome
AF:
0.429
AC:
251446
AN:
585564
Hom.:
55174
Cov.:
7
AF XY:
0.425
AC XY:
132917
AN XY:
312906
show subpopulations
Gnomad4 AFR exome
AF:
0.279
Gnomad4 AMR exome
AF:
0.533
Gnomad4 ASJ exome
AF:
0.366
Gnomad4 EAS exome
AF:
0.330
Gnomad4 SAS exome
AF:
0.371
Gnomad4 FIN exome
AF:
0.467
Gnomad4 NFE exome
AF:
0.446
Gnomad4 OTH exome
AF:
0.419
GnomAD4 genome
AF:
0.391
AC:
59529
AN:
152102
Hom.:
12121
Cov.:
33
AF XY:
0.391
AC XY:
29097
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.281
Gnomad4 AMR
AF:
0.469
Gnomad4 ASJ
AF:
0.368
Gnomad4 EAS
AF:
0.320
Gnomad4 SAS
AF:
0.383
Gnomad4 FIN
AF:
0.458
Gnomad4 NFE
AF:
0.439
Gnomad4 OTH
AF:
0.376
Alfa
AF:
0.424
Hom.:
11932
Bravo
AF:
0.384
Asia WGS
AF:
0.417
AC:
1453
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
3.5
DANN
Benign
0.78

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.

Other links and lift over

dbSNP: rs10781496; hg19: chr9-139261086; COSMIC: COSV59996723; COSMIC: COSV59996723; API