19-48211896-T-C

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.1428A>G(p.Gln476=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,613,698 control chromosomes in the GnomAD database, including 233,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17014 hom., cov: 30)
  • Exomes 𝑓: 0.54 (216351 hom.)
• Consequence: CARD8 NM_001184900.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.706

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=-0.86).
• BP6: Variant 19-48211896-T-C is Benign according to our data. Variant chr19-48211896-T-C is described in ClinVar as [Benign]. Clinvar id is 1168810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.706 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD8	NM_001184900.3	c.1428A>G	p.Gln476=	synonymous_variant	14/14	ENST00000651546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD8	ENST00000651546.1	c.1428A>G	p.Gln476=	synonymous_variant	14/14		NM_001184900.3	A2
	ENST00000595201.2	n.390-1070T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69182 AN: 151790 Hom.: 17017 Cov.: 30

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.485

GnomAD3 exomes AF: 0.502 AC: 126204 AN: 251254 Hom.: 33161 AF XY: 0.508 AC XY: 69061 AN XY: 135834

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.565

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.249

Gnomad SAS exome AF: 0.540

Gnomad FIN exome AF: 0.452

Gnomad NFE exome AF: 0.556

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.539 AC: 788394 AN: 1461788 Hom.: 216351 Cov.: 49 AF XY: 0.540 AC XY: 392904 AN XY: 727206

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.541

Gnomad4 FIN exome AF: 0.461

Gnomad4 NFE exome AF: 0.562

Gnomad4 OTH exome AF: 0.512

GnomAD4 genome AF: 0.456 AC: 69195 AN: 151910 Hom.: 17014 Cov.: 30 AF XY: 0.452 AC XY: 33576 AN XY: 74226

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.487

Alfa AF: 0.530 Hom.: 29234

Bravo AF: 0.451

Asia WGS AF: 0.393 AC: 1369 AN: 3478

EpiCase AF: 0.553

EpiControl AF: 0.553

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

Feb 01, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.8
Dann	Benign	0.52

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: rs3745718; hg19: chr19-48715153; COSMIC: COSV62873792; COSMIC: COSV62873792;