rs972800

Variant names:

• chr19-48186136-T-G
• rs972800
• NM_199341.4:c.588+3369T>G

Variant summary

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

The NM_199341.4(ZSWIM9):​c.588+3369T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,188 control chromosomes in the GnomAD database, including 4,225 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 0.17 (4225 hom., cov: 33)
• Consequence: ZSWIM9 NM_199341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM9	NM_199341.4	c.588+3369T>G		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.588+3369T>G		intron_variant	Intron 3 of 3	5	NM_199341.4	ENSP00000480314.1
ZSWIM9	ENST00000328759.11	c.588+3369T>G		intron_variant	Intron 3 of 4	1		ENSP00000331363.7
CARD8	ENST00000600800.1	n.880+414A>C		intron_variant	Intron 7 of 7	2

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25250 AN: 152070 Hom.: 4213 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0498

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25299 AN: 152188 Hom.: 4225 Cov.: 33 AF XY: 0.164 AC XY: 12230 AN XY: 74434

African (AFR) AF: 0.429 AC: 17799 AN: 41444

American (AMR) AF: 0.0888 AC: 1358 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3470

East Asian (EAS) AF: 0.160 AC: 830 AN: 5188

South Asian (SAS) AF: 0.178 AC: 858 AN: 4824

European-Finnish (FIN) AF: 0.0325 AC: 345 AN: 10620

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0498 AC: 3389 AN: 68032

Other (OTH) AF: 0.142 AC: 300 AN: 2114

Alfa AF: 0.0887 Hom.: 2533

Bravo AF: 0.182

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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: rs972800; hg19: chr19-48689393;