rs11787537

Variant names:

• chr9-90854337-G-A
• rs11787537
• NM_003177.7:c.579-7869G>A

Variant summary

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

The NM_003177.7(SYK):​c.579-7869G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,194 control chromosomes in the GnomAD database, including 2,049 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 0.16 (2049 hom., cov: 31)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.579-7869G>A		intron_variant	Intron 3 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.579-7869G>A		intron_variant	Intron 3 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.579-7869G>A		intron_variant	Intron 3 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.579-7869G>A		intron_variant	Intron 3 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.579-7869G>A		intron_variant	Intron 3 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23906 AN: 152076 Hom.: 2051 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00596

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.157 AC: 23904 AN: 152194 Hom.: 2049 Cov.: 31 AF XY: 0.153 AC XY: 11362 AN XY: 74394

African (AFR) AF: 0.129 AC: 5367 AN: 41526

American (AMR) AF: 0.120 AC: 1840 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3470

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5186

South Asian (SAS) AF: 0.165 AC: 796 AN: 4818

European-Finnish (FIN) AF: 0.116 AC: 1225 AN: 10592

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13406 AN: 67986

Other (OTH) AF: 0.154 AC: 326 AN: 2112

Alfa AF: 0.174 Hom.: 1053

Bravo AF: 0.155

Asia WGS AF: 0.0750 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.77
PhyloP100		1.3
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: rs11787537; hg19: chr9-93616619;