rs12463216

Variant names:

• chr19-48194525-T-A
• rs12463216
• NM_199341.4:c.589-128T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-48194525-T-A
• chr19-48194525-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_199341.4(ZSWIM9):​c.589-128T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZSWIM9 NM_199341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 7 publications found

Genes affected

ZSWIM9 (HGNC:34495): (zinc finger SWIM-type containing 9) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM9	NM_199341.4	c.589-128T>A		intron_variant	Intron 3 of 3	ENST00000614654.2	NP_955373.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM9	ENST00000614654.2	c.589-128T>A		intron_variant	Intron 3 of 3	5	NM_199341.4	ENSP00000480314.1
ZSWIM9	ENST00000328759.11	c.589-128T>A		intron_variant	Intron 3 of 4	1		ENSP00000331363.7
CARD8	ENST00000600800.1	n.110-1344A>T		intron_variant	Intron 1 of 7	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 804482 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 395918

African (AFR) AF: 0.00 AC: 0 AN: 16436

American (AMR) AF: 0.00 AC: 0 AN: 11072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13630

East Asian (EAS) AF: 0.00 AC: 0 AN: 25724

South Asian (SAS) AF: 0.00 AC: 0 AN: 36878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 634086

Other (OTH) AF: 0.00 AC: 0 AN: 36062

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.65
PhyloP100		-0.090

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: rs12463216; hg19: chr19-48697782;