19-48209461-T-C

Variant names:

• chr19-48209461-T-C
• rs4802445
• ENST00000518622.5:n.*3420A>G

Variant summary

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

The ENST00000518622.5(CARD8):​n.*3420A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 151,950 control chromosomes in the GnomAD database, including 16,973 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 0.45 (16970 hom., cov: 32)
  • Exomes 𝑓: 0.88 (3 hom.)
• Consequence: CARD8 ENST00000518622.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• 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)

ENSG00000268583 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518622.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD8	NM_001184900.3	MANE Select	c.*2249A>G		3_prime_UTR	Exon 14 of 14	NP_001171829.1
	CARD8	NR_033678.1		n.3823A>G		non_coding_transcript_exon	Exon 10 of 10
	CARD8	NR_033679.1		n.3865A>G		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD8	ENST00000518622.5	TSL:1	n.*3420A>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000430057.1
	CARD8	ENST00000651546.1	MANE Select	c.*2249A>G		3_prime_UTR	Exon 14 of 14	ENSP00000499211.1
	CARD8	ENST00000391898.7	TSL:1	c.*2249A>G		3_prime_UTR	Exon 11 of 11	ENSP00000375767.3

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69110 AN: 151824 Hom.: 16974 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.875 AC: 7 AN: 8 Hom.: 3 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.455 AC: 69121 AN: 151942 Hom.: 16970 Cov.: 32 AF XY: 0.452 AC XY: 33539 AN XY: 74250

African (AFR) AF: 0.264 AC: 10948 AN: 41446

American (AMR) AF: 0.543 AC: 8281 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1861 AN: 3466

East Asian (EAS) AF: 0.255 AC: 1321 AN: 5182

South Asian (SAS) AF: 0.540 AC: 2604 AN: 4824

European-Finnish (FIN) AF: 0.451 AC: 4748 AN: 10520

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.556 AC: 37780 AN: 67940

Other (OTH) AF: 0.485 AC: 1024 AN: 2110

Alfa AF: 0.520 Hom.: 25866

Bravo AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.73
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4802445; hg19: chr19-48712718;