chr19-48211908-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_001184900.3(CARD8):c.1416C>T(p.Leu472=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0022 in 1,613,896 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.012 ( 39 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 33 hom. )
Consequence
CARD8
NM_001184900.3 synonymous
NM_001184900.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.695
Genes affected
CARD8 (HGNC:17057): (caspase recruitment domain family member 8) The protein encoded by this gene belongs to the caspase recruitment domain (CARD)-containing family of proteins, which are involved in pathways leading to activation of caspases or nuclear factor kappa-B (NFKB). This protein may be a component of the inflammasome, a protein complex that plays a role in the activation of proinflammatory caspases. It is thought that this protein acts as an adaptor molecule that negatively regulates NFKB activation, CASP1-dependent IL1B secretion, and apoptosis. Polymorphisms in this gene may be associated with a susceptibility to rheumatoid arthritis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
?
Variant 19-48211908-G-A is Benign according to our data. Variant chr19-48211908-G-A is described in ClinVar as [Benign]. Clinvar id is 782653.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.695 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1758/152090) while in subpopulation AFR AF= 0.0384 (1592/41462). AF 95% confidence interval is 0.0368. There are 39 homozygotes in gnomad4. There are 821 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1756 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD8 | NM_001184900.3 | c.1416C>T | p.Leu472= | synonymous_variant | 14/14 | ENST00000651546.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD8 | ENST00000651546.1 | c.1416C>T | p.Leu472= | synonymous_variant | 14/14 | NM_001184900.3 | A2 | ||
ENST00000595201.2 | n.390-1058G>A | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0116 AC: 1756AN: 151972Hom.: 39 Cov.: 32
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GnomAD3 exomes AF: 0.00299 AC: 751AN: 250884Hom.: 17 AF XY: 0.00207 AC XY: 281AN XY: 135650
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GnomAD4 exome AF: 0.00123 AC: 1799AN: 1461806Hom.: 33 Cov.: 36 AF XY: 0.00107 AC XY: 780AN XY: 727220
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at