rs2115485

Positions:

• chr9-90806972-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):​c.-42+5079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,150 control chromosomes in the GnomAD database, including 4,202 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 0.23 (4202 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.438

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.-42+5079C>T		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.-42+5079C>T		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375747.5	c.-42+4967C>T		intron_variant		1
SYK	ENST00000375751.8	c.-42+5079C>T		intron_variant		1
SYK	ENST00000476708.1	n.78+4933C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35481 AN: 152032 Hom.: 4200 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.233 AC: 35504 AN: 152150 Hom.: 4202 Cov.: 33 AF XY: 0.232 AC XY: 17283 AN XY: 74392

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.239

Alfa AF: 0.247 Hom.: 2068

Bravo AF: 0.234

Asia WGS AF: 0.201 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.81

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: rs2115485; hg19: chr9-93569254;