rs290203

Variant names:

• chr9-90858681-G-A
• rs290203
• NM_003177.7:c.579-3525G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-90858681-G-A
• chr9-90858681-G-C
• chr9-90858681-G-T

Variant summary

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

The NM_003177.7(SYK):​c.579-3525G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,216 control chromosomes in the GnomAD database, including 44,358 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 0.76 (44358 hom., cov: 34)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 3 publications found

Genes affected

SYK (HGNC:11491): (spleen associated tyrosine kinase) This gene encodes a member of the family of non-receptor type Tyr protein kinases. This protein is widely expressed in hematopoietic cells and is involved in coupling activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. It is thought to be a modulator of epithelial cell growth and a potential tumour suppressor in human breast carcinomas. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

SYK Gene-Disease associations (from GenCC):

• immunodeficiency 82 with systemic inflammation

  Inheritance: AD Classification: STRONG 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.579-3525G>A		intron_variant	Intron 3 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.579-3525G>A		intron_variant	Intron 3 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.579-3525G>A		intron_variant	Intron 3 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.579-3525G>A		intron_variant	Intron 3 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.579-3525G>A		intron_variant	Intron 3 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.756 AC: 115017 AN: 152098 Hom.: 44316 Cov.: 34

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.756 AC: 115116 AN: 152216 Hom.: 44358 Cov.: 34 AF XY: 0.758 AC XY: 56415 AN XY: 74396

African (AFR) AF: 0.872 AC: 36264 AN: 41568

American (AMR) AF: 0.800 AC: 12239 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2379 AN: 3472

East Asian (EAS) AF: 0.950 AC: 4932 AN: 5190

South Asian (SAS) AF: 0.821 AC: 3966 AN: 4828

European-Finnish (FIN) AF: 0.606 AC: 6401 AN: 10564

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.681 AC: 46312 AN: 67968

Other (OTH) AF: 0.767 AC: 1620 AN: 2112

Alfa AF: 0.735 Hom.: 12685

Bravo AF: 0.778

Asia WGS AF: 0.893 AC: 3105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.013
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: rs290203; hg19: chr9-93620963;