19-48245971-A-G

Position:

• chr19-48245971-A-G

Variant summary

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

The NM_001184900.3(CARD8):​c.-44+3552T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,238 control chromosomes in the GnomAD database, including 30,310 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 0.63 (30310 hom., cov: 31)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.31

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD8	NM_001184900.3	c.-44+3552T>C		intron_variant		ENST00000651546.1	NP_001171829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD8	ENST00000651546.1	c.-44+3552T>C		intron_variant			NM_001184900.3	ENSP00000499211.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 94690 AN: 151154 Hom.: 30285 Cov.: 31

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.632

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.660

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.626 AC: 94749 AN: 151238 Hom.: 30310 Cov.: 31 AF XY: 0.625 AC XY: 46139 AN XY: 73854

Gnomad4 AFR AF: 0.762

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.632

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.561

Gnomad4 OTH AF: 0.634

Alfa AF: 0.593 Hom.: 9311

Bravo AF: 0.640

Asia WGS AF: 0.690 AC: 2399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.014
DANN	Benign	0.45

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: rs6509368; hg19: chr19-48749228;