rs290227

Variant names:

• chr9-90874382-G-A
• rs290227
• NM_003177.7:c.1003+91G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-90874382-G-A
• chr9-90874382-G-C
• chr9-90874382-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003177.7(SYK):​c.1003+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,280,998 control chromosomes in the GnomAD database, including 58,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7513 hom., cov: 32)
  • Exomes 𝑓: 0.29 (51262 hom.)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.329
• Publications: 22 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-90874382-G-A is Benign according to our data. Variant chr9-90874382-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688172.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.1003+91G>A		intron_variant	Intron 8 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.1003+91G>A		intron_variant	Intron 8 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.1003+91G>A		intron_variant	Intron 8 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.934+91G>A		intron_variant	Intron 7 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.934+91G>A		intron_variant	Intron 7 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45863 AN: 151846 Hom.: 7503 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.287 AC: 324445 AN: 1129036 Hom.: 51262 AF XY: 0.294 AC XY: 167760 AN XY: 570486

African (AFR) AF: 0.356 AC: 9594 AN: 26958

American (AMR) AF: 0.243 AC: 9785 AN: 40324

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 5632 AN: 23604

East Asian (EAS) AF: 0.604 AC: 22543 AN: 37328

South Asian (SAS) AF: 0.483 AC: 37510 AN: 77660

European-Finnish (FIN) AF: 0.330 AC: 16233 AN: 49240

Middle Eastern (MID) AF: 0.277 AC: 1410 AN: 5096

European-Non Finnish (NFE) AF: 0.252 AC: 206839 AN: 819468

Other (OTH) AF: 0.302 AC: 14899 AN: 49358

GnomAD4 genome AF: 0.302 AC: 45920 AN: 151962 Hom.: 7513 Cov.: 32 AF XY: 0.311 AC XY: 23059 AN XY: 74242

African (AFR) AF: 0.351 AC: 14527 AN: 41442

American (AMR) AF: 0.247 AC: 3770 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 820 AN: 3466

East Asian (EAS) AF: 0.600 AC: 3083 AN: 5136

South Asian (SAS) AF: 0.507 AC: 2439 AN: 4808

European-Finnish (FIN) AF: 0.345 AC: 3630 AN: 10534

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.246 AC: 16723 AN: 67978

Other (OTH) AF: 0.271 AC: 573 AN: 2112

Alfa AF: 0.265 Hom.: 21820

Bravo AF: 0.297

Asia WGS AF: 0.526 AC: 1827 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 43% of patients studied by a panel of primary immunodeficiencies. Number of patients: 41. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.66
PhyloP100		-0.33
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: rs290227; hg19: chr9-93636664;