19-48238810-T-C

Position:

• chr19-48238810-T-C

Variant summary

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

The NM_001184900.3(CARD8):​c.60-278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,992 control chromosomes in the GnomAD database, including 36,813 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 0.69 (36813 hom., cov: 31)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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 (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD8	NM_001184900.3	c.60-278A>G		intron_variant		ENST00000651546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD8	ENST00000651546.1	c.60-278A>G		intron_variant			NM_001184900.3	A2

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105554 AN: 151874 Hom.: 36786 Cov.: 31

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.598

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.665

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.695 AC: 105629 AN: 151992 Hom.: 36813 Cov.: 31 AF XY: 0.697 AC XY: 51758 AN XY: 74310

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.598

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.665

Gnomad4 OTH AF: 0.699

Alfa AF: 0.676 Hom.: 16972

Bravo AF: 0.701

Asia WGS AF: 0.764 AC: 2650 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.31
DANN	Benign	0.42

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: rs6509364; hg19: chr19-48742067;