19-48240907-C-T

Variant names:

• chr19-48240907-C-T
• rs11670259
• NM_001184900.3:c.59+55G>A

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+55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,351,774 control chromosomes in the GnomAD database, including 73,272 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 0.29 (6857 hom., cov: 31)
  • Exomes 𝑓: 0.33 (66415 hom.)
• Consequence: CARD8 NM_001184900.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 9 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.349 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+55G>A		intron	N/A	NP_001171829.1
	CARD8	NM_001351782.2		c.59+55G>A		intron	N/A	NP_001338711.1
	CARD8	NM_001184901.1		c.59+55G>A		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+55G>A		intron	N/A	ENSP00000499211.1
	CARD8	ENST00000391898.7	TSL:1	c.59+55G>A		intron	N/A	ENSP00000375767.3
	CARD8	ENST00000520153.5	TSL:1	c.59+55G>A		intron	N/A	ENSP00000428736.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44534 AN: 151868 Hom.: 6854 Cov.: 31

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.329 AC: 395255 AN: 1199788 Hom.: 66415 AF XY: 0.330 AC XY: 198211 AN XY: 600774

African (AFR) AF: 0.201 AC: 5597 AN: 27908

American (AMR) AF: 0.401 AC: 14011 AN: 34968

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 7756 AN: 23976

East Asian (EAS) AF: 0.234 AC: 8195 AN: 35014

South Asian (SAS) AF: 0.325 AC: 24465 AN: 75244

European-Finnish (FIN) AF: 0.283 AC: 9549 AN: 33788

Middle Eastern (MID) AF: 0.248 AC: 1332 AN: 5368

European-Non Finnish (NFE) AF: 0.338 AC: 308026 AN: 911774

Other (OTH) AF: 0.315 AC: 16324 AN: 51748

GnomAD4 genome AF: 0.293 AC: 44562 AN: 151986 Hom.: 6857 Cov.: 31 AF XY: 0.291 AC XY: 21632 AN XY: 74292

African (AFR) AF: 0.211 AC: 8755 AN: 41454

American (AMR) AF: 0.357 AC: 5447 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3468

East Asian (EAS) AF: 0.216 AC: 1121 AN: 5180

South Asian (SAS) AF: 0.326 AC: 1569 AN: 4820

European-Finnish (FIN) AF: 0.263 AC: 2779 AN: 10552

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22837 AN: 67944

Other (OTH) AF: 0.295 AC: 622 AN: 2108

Alfa AF: 0.322 Hom.: 17378

Bravo AF: 0.295

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.025
DANN	Benign	0.52
PhyloP100		-1.8
PromoterAI		-0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11670259; hg19: chr19-48744164; COSMIC: COSV62873104;