chr19-48240212-A-G

Position:

• chr19-48240212-A-G

Variant summary

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

The NM_001184900.3(CARD8):​c.59+750T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,084 control chromosomes in the GnomAD database, including 8,963 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 0.34 (8963 hom., cov: 31)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.59+750T>C		intron_variant		ENST00000651546.1	NP_001171829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD8	ENST00000651546.1	c.59+750T>C		intron_variant			NM_001184900.3	ENSP00000499211	A2

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51836 AN: 151966 Hom.: 8964 Cov.: 31

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51859 AN: 152084 Hom.: 8963 Cov.: 31 AF XY: 0.345 AC XY: 25654 AN XY: 74336

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.273

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.344

Alfa AF: 0.331 Hom.: 4769

Bravo AF: 0.335

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6509365; hg19: chr19-48743469;