Variant 19-48211896-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.706

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	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 linkuse as main transcript	c.1428A>G	p.Gln476=	synonymous_variant	14/14		NM_001184900.3	A2	Q9Y2G2-5
	ENST00000595201.2 linkuse as main transcript	n.390-1070T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69182

AN:

151790

Hom.:

17017

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.540

AC XY:

392904

AN XY:

727206

show subpopulations

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.:

AF XY:

0.452

AC XY:

33576

AN XY:

74226

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over