19-48242052-G-T

Variant names:

• chr19-48242052-G-T
• rs12984929
• NM_001184900.3:c.-43-989C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184900.3(CARD8):​c.-43-989C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,322 control chromosomes in the GnomAD database, including 11,571 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 0.39 (11571 hom., cov: 31)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818
• Publications: 6 publications found

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]

CARD8 Gene-Disease associations (from GenCC):

• inflammatory bowel disease 30

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.-43-989C>A		intron_variant	Intron 3 of 13	ENST00000651546.1	NP_001171829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD8	ENST00000651546.1	c.-43-989C>A		intron_variant	Intron 3 of 13		NM_001184900.3	ENSP00000499211.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59282 AN: 151208 Hom.: 11566 Cov.: 31

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.392 AC: 59310 AN: 151322 Hom.: 11571 Cov.: 31 AF XY: 0.392 AC XY: 29016 AN XY: 73938

African (AFR) AF: 0.369 AC: 15180 AN: 41182

American (AMR) AF: 0.441 AC: 6703 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1375 AN: 3456

East Asian (EAS) AF: 0.372 AC: 1916 AN: 5146

South Asian (SAS) AF: 0.415 AC: 1988 AN: 4794

European-Finnish (FIN) AF: 0.334 AC: 3508 AN: 10488

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.405 AC: 27468 AN: 67740

Other (OTH) AF: 0.397 AC: 833 AN: 2098

Alfa AF: 0.396 Hom.: 13462

Bravo AF: 0.395

Asia WGS AF: 0.418 AC: 1452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.69
DANN	Benign	0.78
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12984929; hg19: chr19-48745309;