rs2043211

Variant names:

• chr19-48234449-A-T
• rs2043211
• NM_001184900.3:c.304T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-48234449-A-T
• chr19-48234449-A-C
• chr19-48234449-A-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001351784.2(CARD8):​c.30T>A​(p.Cys10*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,612,308 control chromosomes in the GnomAD database, including 86,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7120 hom., cov: 32)
  • Exomes 𝑓: 0.33 (79001 hom.)
• Consequence: CARD8 NM_001351784.2 stop_gained
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.23
• Publications: 255 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 -16 ACMG points.

• BP6: Variant 19-48234449-A-T is Benign according to our data. Variant chr19-48234449-A-T is described in ClinVar as Benign. ClinVar VariationId is 1166485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351784.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD8	NM_001184900.3	MANE Select	c.304T>A	p.Phe102Ile	missense	Exon 6 of 14	NP_001171829.1	Q9Y2G2-5
	CARD8	NM_001351784.2		c.30T>A	p.Cys10*	stop_gained	Exon 5 of 12	NP_001338713.1
	CARD8	NM_001365950.1		c.30T>A	p.Cys10*	stop_gained	Exon 4 of 11	NP_001352879.1	Q9Y2G2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD8	ENST00000651546.1	MANE Select	c.304T>A	p.Phe102Ile	missense	Exon 6 of 14	ENSP00000499211.1	Q9Y2G2-5
	CARD8	ENST00000391898.7	TSL:1	c.304T>A	p.Phe102Ile	missense	Exon 3 of 11	ENSP00000375767.3	Q9Y2G2-5
	CARD8	ENST00000520153.5	TSL:1	c.154T>A	p.Phe52Ile	missense	Exon 4 of 12	ENSP00000428736.1	Q9Y2G2-4

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45296 AN: 151914 Hom.: 7119 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.308

GnomAD2 exomes AF: 0.327 AC: 82112 AN: 250934 AF XY: 0.331

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.255

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.508

Gnomad FIN exome AF: 0.368

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.320

GnomAD4 exome AF: 0.326 AC: 475366 AN: 1460276 Hom.: 79001 Cov.: 33 AF XY: 0.326 AC XY: 236907 AN XY: 726490

African (AFR) AF: 0.208 AC: 6966 AN: 33450

American (AMR) AF: 0.259 AC: 11547 AN: 44632

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 7054 AN: 26108

East Asian (EAS) AF: 0.447 AC: 17700 AN: 39636

South Asian (SAS) AF: 0.342 AC: 29441 AN: 86138

European-Finnish (FIN) AF: 0.362 AC: 19332 AN: 53406

Middle Eastern (MID) AF: 0.343 AC: 1976 AN: 5762

European-Non Finnish (NFE) AF: 0.325 AC: 361170 AN: 1110812

Other (OTH) AF: 0.334 AC: 20180 AN: 60332

GnomAD4 genome AF: 0.298 AC: 45318 AN: 152032 Hom.: 7120 Cov.: 32 AF XY: 0.302 AC XY: 22432 AN XY: 74302

African (AFR) AF: 0.206 AC: 8561 AN: 41504

American (AMR) AF: 0.287 AC: 4377 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 925 AN: 3466

East Asian (EAS) AF: 0.494 AC: 2546 AN: 5158

South Asian (SAS) AF: 0.330 AC: 1591 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3866 AN: 10556

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22326 AN: 67948

Other (OTH) AF: 0.309 AC: 652 AN: 2108

Alfa AF: 0.323 Hom.: 6173

Bravo AF: 0.288

TwinsUK AF: 0.314 AC: 1164

ALSPAC AF: 0.312 AC: 1203

ESP6500AA AF: 0.209 AC: 919

ESP6500EA AF: 0.329 AC: 2829

ExAC AF: 0.326 AC: 39622

Asia WGS AF: 0.416 AC: 1446 AN: 3478

EpiCase AF: 0.330

EpiControl AF: 0.327

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.15
DANN	Benign	0.86
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.00019	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.025
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.66	P
Vest4		0.15
MPC		0.23
ClinPred		0.0052	T
GERP RS		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=170/30	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: rs2043211; hg19: chr19-48737706; COSMIC: COSV62872790; COSMIC: COSV62872790;