chr9-90839673-G-T

Variant names:

• chr9-90839673-G-T
• rs1864202
• NM_003177.7:c.-41-4185G>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.-41-4185G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,070 control chromosomes in the GnomAD database, including 4,804 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 0.25 (4804 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.774
• Publications: 7 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003177.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.-41-4185G>T		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.-41-4185G>T		intron	N/A	NP_001167638.1
	SYK	NM_001135052.4		c.-41-4185G>T		intron	N/A	NP_001128524.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.-41-4185G>T		intron	N/A	ENSP00000364907.4
	SYK	ENST00000375746.1	TSL:1	c.-41-4185G>T		intron	N/A	ENSP00000364898.1
	SYK	ENST00000375747.5	TSL:1	c.-41-4185G>T		intron	N/A	ENSP00000364899.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37518 AN: 151952 Hom.: 4795 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.247 AC: 37559 AN: 152070 Hom.: 4804 Cov.: 32 AF XY: 0.244 AC XY: 18120 AN XY: 74328

African (AFR) AF: 0.198 AC: 8231 AN: 41480

American (AMR) AF: 0.227 AC: 3462 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3466

East Asian (EAS) AF: 0.136 AC: 705 AN: 5182

South Asian (SAS) AF: 0.295 AC: 1419 AN: 4818

European-Finnish (FIN) AF: 0.226 AC: 2389 AN: 10566

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19661 AN: 67970

Other (OTH) AF: 0.241 AC: 510 AN: 2114

Alfa AF: 0.270 Hom.: 10242

Bravo AF: 0.241

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.68
PhyloP100		0.77
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: rs1864202; hg19: chr9-93601955;