9-90867507-C-G

Variant names:

• chr9-90867507-C-G
• rs965892
• NM_003177.7:c.915+308C>G

Variant summary

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

The NM_003177.7(SYK):​c.915+308C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,248 control chromosomes in the GnomAD database, including 54,716 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 0.84 (54716 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.915+308C>G		intron_variant	Intron 7 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.915+308C>G		intron_variant	Intron 7 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.915+308C>G		intron_variant	Intron 7 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.846+2410C>G		intron_variant	Intron 6 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.846+2410C>G		intron_variant	Intron 6 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128494 AN: 152130 Hom.: 54670 Cov.: 33

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.845 AC: 128597 AN: 152248 Hom.: 54716 Cov.: 33 AF XY: 0.848 AC XY: 63139 AN XY: 74418

African (AFR) AF: 0.932 AC: 38718 AN: 41552

American (AMR) AF: 0.863 AC: 13209 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2978 AN: 3470

East Asian (EAS) AF: 0.954 AC: 4950 AN: 5186

South Asian (SAS) AF: 0.856 AC: 4130 AN: 4824

European-Finnish (FIN) AF: 0.810 AC: 8575 AN: 10582

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53104 AN: 68018

Other (OTH) AF: 0.858 AC: 1812 AN: 2112

Alfa AF: 0.745 Hom.: 2193

Bravo AF: 0.854

Asia WGS AF: 0.916 AC: 3186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.078
DANN	Benign	0.33
PhyloP100		-1.9
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: rs965892; hg19: chr9-93629789;