19-48240907-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184900.3(CARD8):c.59+55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,351,774 control chromosomes in the GnomAD database, including 73,272 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 0.29 (6857 hom., cov: 31)
  • Exomes 𝑓: 0.33 (66415 hom.)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD8	NM_001184900.3	c.59+55G>A		intron_variant		ENST00000651546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD8	ENST00000651546.1	c.59+55G>A		intron_variant			NM_001184900.3	A2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44534 AN: 151868 Hom.: 6854 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.329 AC: 395255 AN: 1199788 Hom.: 66415 AF XY: 0.330 AC XY: 198211 AN XY: 600774

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.401

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.325

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.293 AC: 44562 AN: 151986 Hom.: 6857 Cov.: 31 AF XY: 0.291 AC XY: 21632 AN XY: 74292

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.295

Alfa AF: 0.324 Hom.: 11575

Bravo AF: 0.295

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.025
Dann	Benign	0.52

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

Other links and lift over

dbSNP: rs11670259; hg19: chr19-48744164; COSMIC: COSV62873104;