9-90817715-A-G

Variant names:

• chr9-90817715-A-G
• rs4744505
• NM_003177.7:c.-42+15822A>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.-42+15822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 151,890 control chromosomes in the GnomAD database, including 31,839 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 0.65 (31839 hom., cov: 31)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590
• Publications: 8 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: PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.689 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.-42+15822A>G		intron	N/A	NP_003168.2
	SYK	NM_001135052.4		c.-42+15822A>G		intron	N/A	NP_001128524.1	P43405-2
	SYK	NM_001174168.3		c.-42+15710A>G		intron	N/A	NP_001167639.1	P43405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.-42+15822A>G		intron	N/A	ENSP00000364907.4	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.-42+15710A>G		intron	N/A	ENSP00000364899.1	P43405-2
	SYK	ENST00000375751.8	TSL:1	c.-42+15822A>G		intron	N/A	ENSP00000364904.4	P43405-2

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98101 AN: 151770 Hom.: 31788 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.647 AC: 98219 AN: 151890 Hom.: 31839 Cov.: 31 AF XY: 0.646 AC XY: 47940 AN XY: 74226

African (AFR) AF: 0.598 AC: 24738 AN: 41370

American (AMR) AF: 0.700 AC: 10686 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2276 AN: 3470

East Asian (EAS) AF: 0.567 AC: 2923 AN: 5156

South Asian (SAS) AF: 0.680 AC: 3274 AN: 4814

European-Finnish (FIN) AF: 0.586 AC: 6173 AN: 10536

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 45981 AN: 67960

Other (OTH) AF: 0.673 AC: 1419 AN: 2108

Alfa AF: 0.668 Hom.: 56870

Bravo AF: 0.647

Asia WGS AF: 0.663 AC: 2306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.86
PhyloP100		-0.059
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4744505;

hg19: chr9-93579997;