rs3789889

chr9-90809059-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):c.-42+7166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,136 control chromosomes in the GnomAD database, including 9,795 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 0.36 (9795 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.-42+7166A>G		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.-42+7166A>G		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375747.5	c.-42+7054A>G		intron_variant		1
SYK	ENST00000375751.8	c.-42+7166A>G		intron_variant		1
SYK	ENST00000476708.1	n.78+7020A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54103 AN: 152018 Hom.: 9773 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.356 AC: 54166 AN: 152136 Hom.: 9795 Cov.: 32 AF XY: 0.357 AC XY: 26580 AN XY: 74372

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.375

Alfa AF: 0.355 Hom.: 12607

Bravo AF: 0.365

Asia WGS AF: 0.373 AC: 1296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	11
Dann	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs3789889; hg19: chr9-93571341;