rs1972619

Variant names:

• chr19-48247672-C-T
• rs1972619
• NM_001184900.3:c.-44+1851G>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.-44+1851G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 150,956 control chromosomes in the GnomAD database, including 2,071 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 0.16 (2071 hom., cov: 31)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• Publications: 9 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.-44+1851G>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.-44+1851G>A		intron_variant	Intron 3 of 13		NM_001184900.3	ENSP00000499211.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24392 AN: 150848 Hom.: 2076 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.162 AC: 24406 AN: 150956 Hom.: 2071 Cov.: 31 AF XY: 0.163 AC XY: 12007 AN XY: 73692

African (AFR) AF: 0.132 AC: 5420 AN: 41214

American (AMR) AF: 0.172 AC: 2599 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 654 AN: 3466

East Asian (EAS) AF: 0.326 AC: 1674 AN: 5136

South Asian (SAS) AF: 0.262 AC: 1256 AN: 4798

European-Finnish (FIN) AF: 0.133 AC: 1357 AN: 10170

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10767 AN: 67736

Other (OTH) AF: 0.177 AC: 370 AN: 2094

Alfa AF: 0.157 Hom.: 251

Bravo AF: 0.160

Asia WGS AF: 0.280 AC: 960 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.31
PhyloP100		-1.4
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: rs1972619; hg19: chr19-48750929;