chr19-48244746-C-A

Position:

• chr19-48244746-C-A

Variant summary

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

The NM_001184900.3(CARD8):​c.-43-3683G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,062 control chromosomes in the GnomAD database, including 454 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 0.072 (454 hom., cov: 32)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD8	NM_001184900.3	c.-43-3683G>T		intron_variant		ENST00000651546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD8	ENST00000651546.1	c.-43-3683G>T		intron_variant			NM_001184900.3	A2

Frequencies

GnomAD3 genomes AF: 0.0716 AC: 10881 AN: 151944 Hom.: 454 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0597

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0922

Gnomad OTH AF: 0.0678

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

GnomAD4 genome AF: 0.0717 AC: 10897 AN: 152062 Hom.: 454 Cov.: 32 AF XY: 0.0690 AC XY: 5128 AN XY: 74338

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0331

Gnomad4 FIN AF: 0.0597

Gnomad4 NFE AF: 0.0922

Gnomad4 OTH AF: 0.0671

Alfa AF: 0.0663 Hom.: 78

Bravo AF: 0.0750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.49

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: rs10500300; hg19: chr19-48748003;