rs290227

Positions:

• chr9-90874382-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
SYK	NM_003177.7	c.1003+91G>A		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.1003+91G>A		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375746.1	c.1003+91G>A		intron_variant		1		P1
SYK	ENST00000375747.5	c.934+91G>A		intron_variant		1
SYK	ENST00000375751.8	c.934+91G>A		intron_variant		1

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

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.604

Gnomad4 SAS exome AF: 0.483

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.302

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

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.271

Alfa AF: 0.256 Hom.: 8763

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs290227; hg19: chr9-93636664;