rs17489214

Variant names:

• chr9-90840856-G-A
• rs17489214
• NM_003177.7:c.-41-3002G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-90840856-G-A
• chr9-90840856-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.-41-3002G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,206 control chromosomes in the GnomAD database, including 2,131 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 0.16 (2131 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.-41-3002G>A		intron_variant	Intron 1 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.-41-3002G>A		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24103 AN: 152088 Hom.: 2132 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.158 AC: 24111 AN: 152206 Hom.: 2131 Cov.: 32 AF XY: 0.154 AC XY: 11451 AN XY: 74414

African (AFR) AF: 0.118 AC: 4911 AN: 41530

American (AMR) AF: 0.136 AC: 2086 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3470

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5182

South Asian (SAS) AF: 0.164 AC: 792 AN: 4826

European-Finnish (FIN) AF: 0.118 AC: 1245 AN: 10588

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13631 AN: 68004

Other (OTH) AF: 0.163 AC: 343 AN: 2110

Alfa AF: 0.187 Hom.: 12137

Bravo AF: 0.157

Asia WGS AF: 0.0830 AC: 291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.067
DANN	Benign	0.85
PhyloP100		-1.1
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: rs17489214; hg19: chr9-93603138;