chr19-48240320-G-A

Variant names:

• chr19-48240320-G-A
• rs6509366
• NM_001184900.3:c.59+642C>T

Variant summary

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

The NM_001184900.3(CARD8):​c.59+642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,030 control chromosomes in the GnomAD database, including 7,321 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 0.30 (7321 hom., cov: 31)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 11 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.59+642C>T		intron_variant	Intron 4 of 13	ENST00000651546.1	NP_001171829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD8	ENST00000651546.1	c.59+642C>T		intron_variant	Intron 4 of 13		NM_001184900.3	ENSP00000499211.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46003 AN: 151912 Hom.: 7321 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.303 AC: 46024 AN: 152030 Hom.: 7321 Cov.: 31 AF XY: 0.307 AC XY: 22827 AN XY: 74316

African (AFR) AF: 0.214 AC: 8872 AN: 41476

American (AMR) AF: 0.288 AC: 4400 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3470

East Asian (EAS) AF: 0.494 AC: 2548 AN: 5162

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4816

European-Finnish (FIN) AF: 0.380 AC: 4012 AN: 10562

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22541 AN: 67950

Other (OTH) AF: 0.311 AC: 657 AN: 2110

Alfa AF: 0.321 Hom.: 4694

Bravo AF: 0.291

Asia WGS AF: 0.421 AC: 1462 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	8.3
DANN	Benign	0.57
PhyloP100		0.19
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: rs6509366; hg19: chr19-48743577;