19-48211779-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001184900.3(CARD8):c.1545C>T(p.Asp515=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00771 in 1,614,054 control chromosomes in the GnomAD database, including 832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (431 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (401 hom.)
• Consequence: CARD8 NM_001184900.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.403

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-48211779-G-A is Benign according to our data. Variant chr19-48211779-G-A is described in ClinVar as [Benign]. Clinvar id is 1168809.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.403 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD8	NM_001184900.3	c.1545C>T	p.Asp515=	synonymous_variant	14/14	ENST00000651546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD8	ENST00000651546.1	c.1545C>T	p.Asp515=	synonymous_variant	14/14		NM_001184900.3	A2
	ENST00000595201.2	n.390-1187G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6217 AN: 152072 Hom.: 428 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0296

GnomAD3 exomes AF: 0.0110 AC: 2759 AN: 251428 Hom.: 166 AF XY: 0.00785 AC XY: 1067 AN XY: 135882

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.00824

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000359

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000185

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00425 AC: 6212 AN: 1461864 Hom.: 401 Cov.: 30 AF XY: 0.00357 AC XY: 2597 AN XY: 727236

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.00910

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000383

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000135

Gnomad4 OTH exome AF: 0.00836

GnomAD4 genome AF: 0.0410 AC: 6233 AN: 152190 Hom.: 431 Cov.: 32 AF XY: 0.0389 AC XY: 2893 AN XY: 74406

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0293

Alfa AF: 0.0219 Hom.: 113

Bravo AF: 0.0467

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.4
Dann	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs8112588; hg19: chr19-48715036;