rs4802436

Variant names:

• chr19-48181555-A-G
• rs4802436
• NM_199341.4:c.276-900A>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.276-900A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,278 control chromosomes in the GnomAD database, including 2,097 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 0.15 (2097 hom., cov: 31)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: ZSWIM9 NM_199341.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSWIM9	NM_199341.4	c.276-900A>G		intron_variant	Intron 2 of 3	ENST00000614654.2	NP_955373.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM9	ENST00000614654.2	c.276-900A>G		intron_variant	Intron 2 of 3	5	NM_199341.4	ENSP00000480314.1
ZSWIM9	ENST00000328759.11	c.276-900A>G		intron_variant	Intron 2 of 4	1		ENSP00000331363.7
CARD8	ENST00000600800.1	n.2418T>C		non_coding_transcript_exon_variant	Exon 8 of 8	2

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22271 AN: 152156 Hom.: 2098 Cov.: 31

Gnomad AFR AF: 0.0383

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.0639

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.146 AC: 22261 AN: 152274 Hom.: 2097 Cov.: 31 AF XY: 0.144 AC XY: 10699 AN XY: 74452

African (AFR) AF: 0.0382 AC: 1588 AN: 41574

American (AMR) AF: 0.145 AC: 2216 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 786 AN: 3472

East Asian (EAS) AF: 0.0636 AC: 330 AN: 5186

South Asian (SAS) AF: 0.207 AC: 996 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1528 AN: 10604

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14291 AN: 68004

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.191 Hom.: 6268

Bravo AF: 0.138

Asia WGS AF: 0.0960 AC: 338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.062
DANN	Benign	0.41
PhyloP100		-2.5
Mutation Taster		=100/0	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: rs4802436; hg19: chr19-48684812;