19-48238810-T-C

Variant names:

• chr19-48238810-T-C
• rs6509364
• NM_001184900.3:c.60-278A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 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=-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 rank	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.60-278A>G		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.60-278A>G		intron_variant	Intron 4 of 13		NM_001184900.3	ENSP00000499211.1

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

African (AFR) AF: 0.755 AC: 31285 AN: 41418

American (AMR) AF: 0.702 AC: 10721 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.598 AC: 2071 AN: 3466

East Asian (EAS) AF: 0.748 AC: 3870 AN: 5176

South Asian (SAS) AF: 0.747 AC: 3602 AN: 4822

European-Finnish (FIN) AF: 0.621 AC: 6560 AN: 10568

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.665 AC: 45206 AN: 67952

Other (OTH) AF: 0.699 AC: 1475 AN: 2110

Alfa AF: 0.675 Hom.: 18865

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
PhyloP100		-0.75
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: rs6509364; hg19: chr19-48742067;