chr9-90872131-G-A

Variant names:

• chr9-90872131-G-A
• rs290229
• NM_003177.7:c.916-2073G>A

Variant summary

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

The NM_003177.7(SYK):​c.916-2073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,076 control chromosomes in the GnomAD database, including 4,511 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 0.22 (4511 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003177.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.916-2073G>A		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.916-2073G>A		intron	N/A	NP_001167638.1
	SYK	NM_001135052.4		c.847-2073G>A		intron	N/A	NP_001128524.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.916-2073G>A		intron	N/A	ENSP00000364907.4
	SYK	ENST00000375746.1	TSL:1	c.916-2073G>A		intron	N/A	ENSP00000364898.1
	SYK	ENST00000375747.5	TSL:1	c.847-2073G>A		intron	N/A	ENSP00000364899.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34144 AN: 151958 Hom.: 4506 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.225 AC: 34167 AN: 152076 Hom.: 4511 Cov.: 33 AF XY: 0.232 AC XY: 17212 AN XY: 74350

African (AFR) AF: 0.177 AC: 7343 AN: 41470

American (AMR) AF: 0.183 AC: 2800 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 851 AN: 3466

East Asian (EAS) AF: 0.640 AC: 3310 AN: 5172

South Asian (SAS) AF: 0.374 AC: 1802 AN: 4824

European-Finnish (FIN) AF: 0.258 AC: 2732 AN: 10576

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14484 AN: 67976

Other (OTH) AF: 0.240 AC: 507 AN: 2112

Alfa AF: 0.214 Hom.: 6210

Bravo AF: 0.217

Asia WGS AF: 0.498 AC: 1729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020
DANN	Benign	0.43
PhyloP100		-2.0
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: rs290229; hg19: chr9-93634413; COSMIC: COSV65326234;