rs6509365

Variant names:

• chr19-48240212-A-G
• rs6509365
• NM_001184900.3:c.59+750T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001184900.3(CARD8):​c.59+750T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,084 control chromosomes in the GnomAD database, including 8,963 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 0.34 (8963 hom., cov: 31)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 27 publications found

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 Gene-Disease associations (from GenCC):

• inflammatory bowel disease 30

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001184900.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD8	NM_001184900.3	MANE Select	c.59+750T>C		intron	N/A	NP_001171829.1
	CARD8	NM_001351782.2		c.59+750T>C		intron	N/A	NP_001338711.1
	CARD8	NM_001184901.1		c.59+750T>C		intron	N/A	NP_001171830.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD8	ENST00000651546.1	MANE Select	c.59+750T>C		intron	N/A	ENSP00000499211.1
	CARD8	ENST00000391898.7	TSL:1	c.59+750T>C		intron	N/A	ENSP00000375767.3
	CARD8	ENST00000520153.5	TSL:1	c.59+750T>C		intron	N/A	ENSP00000428736.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51836 AN: 151966 Hom.: 8964 Cov.: 31

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.341 AC: 51859 AN: 152084 Hom.: 8963 Cov.: 31 AF XY: 0.345 AC XY: 25654 AN XY: 74336

African (AFR) AF: 0.338 AC: 14021 AN: 41504

American (AMR) AF: 0.307 AC: 4697 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 945 AN: 3464

East Asian (EAS) AF: 0.497 AC: 2565 AN: 5164

South Asian (SAS) AF: 0.345 AC: 1664 AN: 4818

European-Finnish (FIN) AF: 0.380 AC: 4022 AN: 10574

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.334 AC: 22678 AN: 67958

Other (OTH) AF: 0.344 AC: 728 AN: 2114

Alfa AF: 0.330 Hom.: 5199

Bravo AF: 0.335

Asia WGS AF: 0.432 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.63
DANN	Benign	0.46
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6509365; hg19: chr19-48743469;