chr9-90806385-C-T

Variant names:

• chr9-90806385-C-T
• rs2035072
• NM_003177.7:c.-42+4492C>T

Variant summary

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

The NM_003177.7(SYK):​c.-42+4492C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 151,744 control chromosomes in the GnomAD database, including 67,648 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 0.94 (67648 hom., cov: 29)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.-42+4492C>T		intron_variant	Intron 1 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.-42+4492C>T		intron_variant	Intron 1 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375747.5	c.-42+4380C>T		intron_variant	Intron 1 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.-42+4492C>T		intron_variant	Intron 1 of 12	1		ENSP00000364904.4
SYK	ENST00000476708.1	n.78+4346C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143073 AN: 151634 Hom.: 67589 Cov.: 29

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.962

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.908

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.915

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.944 AC: 143188 AN: 151744 Hom.: 67648 Cov.: 29 AF XY: 0.945 AC XY: 70057 AN XY: 74154

African (AFR) AF: 0.985 AC: 40791 AN: 41394

American (AMR) AF: 0.960 AC: 14654 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.908 AC: 3151 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5169 AN: 5174

South Asian (SAS) AF: 0.958 AC: 4611 AN: 4814

European-Finnish (FIN) AF: 0.915 AC: 9480 AN: 10366

Middle Eastern (MID) AF: 0.969 AC: 283 AN: 292

European-Non Finnish (NFE) AF: 0.915 AC: 62187 AN: 67952

Other (OTH) AF: 0.947 AC: 1985 AN: 2096

Alfa AF: 0.961 Hom.: 9183

Bravo AF: 0.949

Asia WGS AF: 0.983 AC: 3418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.57
DANN	Benign	0.33
PhyloP100		-1.0
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: rs2035072; hg19: chr9-93568667;