19-48222166-T-C

Variant names:

• chr19-48222166-T-C
• rs16981829
• NM_001184900.3:c.1036-311A>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.1036-311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,154 control chromosomes in the GnomAD database, including 6,461 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 0.28 (6461 hom., cov: 32)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.920
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.1036-311A>G		intron_variant	Intron 10 of 13	ENST00000651546.1	NP_001171829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD8	ENST00000651546.1	c.1036-311A>G		intron_variant	Intron 10 of 13		NM_001184900.3	ENSP00000499211.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42639 AN: 152036 Hom.: 6459 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.280 AC: 42655 AN: 152154 Hom.: 6461 Cov.: 32 AF XY: 0.284 AC XY: 21122 AN XY: 74390

African (AFR) AF: 0.162 AC: 6716 AN: 41502

American (AMR) AF: 0.264 AC: 4036 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 894 AN: 3470

East Asian (EAS) AF: 0.486 AC: 2517 AN: 5176

South Asian (SAS) AF: 0.320 AC: 1547 AN: 4830

European-Finnish (FIN) AF: 0.377 AC: 3985 AN: 10582

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21938 AN: 67996

Other (OTH) AF: 0.290 AC: 611 AN: 2110

Alfa AF: 0.301 Hom.: 9023

Bravo AF: 0.266

Asia WGS AF: 0.401 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.92
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: rs16981829; hg19: chr19-48725423;