19-48214075-T-C

Position:

• chr19-48214075-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184900.3(CARD8):​c.1348+1265A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.861 in 152,176 control chromosomes in the GnomAD database, including 56,633 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 0.86 (56633 hom., cov: 33)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.655

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.1348+1265A>G		intron_variant		ENST00000651546.1	NP_001171829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD8	ENST00000651546.1	c.1348+1265A>G		intron_variant			NM_001184900.3	ENSP00000499211	A2
	ENST00000595201.2	n.1499T>C		non_coding_transcript_exon_variant	3/3	4

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130983 AN: 152058 Hom.: 56603 Cov.: 33

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.861 AC: 131065 AN: 152176 Hom.: 56633 Cov.: 33 AF XY: 0.858 AC XY: 63868 AN XY: 74402

Gnomad4 AFR AF: 0.798

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.825

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.905

Gnomad4 OTH AF: 0.874

Alfa AF: 0.893 Hom.: 80568

Bravo AF: 0.858

Asia WGS AF: 0.857 AC: 2981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1966625; hg19: chr19-48717332;