rs1870660

Variant names:

• chr9-90835723-C-G
• rs1870660
• NM_003177.7:c.-41-8135C>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.-41-8135C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,210 control chromosomes in the GnomAD database, including 2,145 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 0.17 (2145 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.-41-8135C>G		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.-41-8135C>G		intron	N/A	NP_001167638.1	P43405-1
	SYK	NM_001135052.4		c.-41-8135C>G		intron	N/A	NP_001128524.1	P43405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.-41-8135C>G		intron	N/A	ENSP00000364907.4	P43405-1
	SYK	ENST00000375746.1	TSL:1	c.-41-8135C>G		intron	N/A	ENSP00000364898.1	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.-41-8135C>G		intron	N/A	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25326 AN: 152092 Hom.: 2142 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.167 AC: 25354 AN: 152210 Hom.: 2145 Cov.: 32 AF XY: 0.165 AC XY: 12314 AN XY: 74406

African (AFR) AF: 0.165 AC: 6841 AN: 41532

American (AMR) AF: 0.131 AC: 1996 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3472

East Asian (EAS) AF: 0.126 AC: 652 AN: 5176

South Asian (SAS) AF: 0.225 AC: 1082 AN: 4818

European-Finnish (FIN) AF: 0.133 AC: 1412 AN: 10608

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12260 AN: 67996

Other (OTH) AF: 0.152 AC: 321 AN: 2110

Alfa AF: 0.176 Hom.: 313

Bravo AF: 0.164

Asia WGS AF: 0.168 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.44
DANN	Benign	0.79
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: rs1870660; hg19: chr9-93598005;