chr19-48194525-T-C

Variant names:

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

Variant summary

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

The NM_199341.4(ZSWIM9):​c.589-128T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 953,740 control chromosomes in the GnomAD database, including 100,133 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 0.46 (16199 hom., cov: 33)
  • Exomes 𝑓: 0.45 (83934 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199341.4. 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
	ZSWIM9	NM_199341.4	MANE Select	c.589-128T>C		intron	N/A	NP_955373.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSWIM9	ENST00000614654.2	TSL:5 MANE Select	c.589-128T>C		intron	N/A	ENSP00000480314.1
	ZSWIM9	ENST00000328759.11	TSL:1	c.589-128T>C		intron	N/A	ENSP00000331363.7
	CARD8	ENST00000600800.1	TSL:2	n.110-1344A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69521 AN: 151960 Hom.: 16188 Cov.: 33

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.516

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.436

GnomAD4 exome AF: 0.453 AC: 363442 AN: 801662 Hom.: 83934 AF XY: 0.454 AC XY: 179240 AN XY: 394592

African (AFR) AF: 0.509 AC: 8324 AN: 16364

American (AMR) AF: 0.478 AC: 5271 AN: 11038

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 6862 AN: 13588

East Asian (EAS) AF: 0.380 AC: 9773 AN: 25686

South Asian (SAS) AF: 0.483 AC: 17728 AN: 36724

European-Finnish (FIN) AF: 0.330 AC: 9237 AN: 27966

Middle Eastern (MID) AF: 0.457 AC: 1180 AN: 2584

European-Non Finnish (NFE) AF: 0.457 AC: 288669 AN: 631732

Other (OTH) AF: 0.456 AC: 16398 AN: 35980

GnomAD4 genome AF: 0.458 AC: 69577 AN: 152078 Hom.: 16199 Cov.: 33 AF XY: 0.450 AC XY: 33437 AN XY: 74360

African (AFR) AF: 0.498 AC: 20657 AN: 41494

American (AMR) AF: 0.486 AC: 7425 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1743 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1689 AN: 5142

South Asian (SAS) AF: 0.471 AC: 2271 AN: 4818

European-Finnish (FIN) AF: 0.303 AC: 3207 AN: 10576

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.457 AC: 31067 AN: 67976

Other (OTH) AF: 0.439 AC: 927 AN: 2112

Alfa AF: 0.464 Hom.: 21014

Bravo AF: 0.469

Asia WGS AF: 0.407 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.41
PhyloP100		-0.090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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; COSMIC: COSV60889663; COSMIC: COSV60889663;