Genetic Variant ZSWIM9:c.589-128T>C (chr19-48194525-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900

Variant links:

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]

ZSWIM9 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM9	NM_199341.4 link	c.589-128T>C		intron_variant	Intron 3 of 3	ENST00000614654.2	NP_955373.3	Q86XI8-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZSWIM9	ENST00000614654.2 link	c.589-128T>C	intron_variant	Intron 3 of 3	5	NM_199341.4	ENSP00000480314.1	Q86XI8-2
ZSWIM9	ENST00000328759.11 link	c.589-128T>C	intron_variant	Intron 3 of 4	1		ENSP00000331363.7	Q86XI8-1
CARD8	ENST00000600800.1 link	n.110-1344A>G	intron_variant	Intron 1 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.457

AC:

69521

AN:

151960

Hom.:

16188

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.509

Gnomad4 AMR exome

AF:

0.478

Gnomad4 ASJ exome

AF:

0.505

Gnomad4 EAS exome

AF:

0.380

Gnomad4 SAS exome

AF:

0.483

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.457

Gnomad4 OTH exome

AF:

0.456

GnomAD4 genome

AF:

0.458

AC:

69577

AN:

152078

Hom.:

16199

Cov.:

AF XY:

0.450

AC XY:

33437

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.498

Gnomad4 AMR

AF:

0.486

Gnomad4 ASJ

AF:

0.502

Gnomad4 EAS

AF:

0.328

Gnomad4 SAS

AF:

0.471

Gnomad4 FIN

AF:

0.303

Gnomad4 NFE

AF:

0.457

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.459

Hom.:

9372

Bravo

AF:

0.469

Asia WGS

AF:

0.407

AC:

1420

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.6

DANN

Benign

0.41

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over