rs1319677

Positions:

• chr9-90803717-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+1824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 151,936 control chromosomes in the GnomAD database, including 13,993 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 0.41 (13993 hom., cov: 31)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYK	NM_003177.7	c.-42+1824A>G		intron_variant		ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.-42+1824A>G		intron_variant		1	NM_003177.7	ENSP00000364907	P1
SYK	ENST00000375747.5	c.-42+1712A>G		intron_variant		1		ENSP00000364899
SYK	ENST00000375751.8	c.-42+1824A>G		intron_variant		1		ENSP00000364904
SYK	ENST00000476708.1	n.78+1678A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62710 AN: 151816 Hom.: 13996 Cov.: 31

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.413 AC: 62730 AN: 151936 Hom.: 13993 Cov.: 31 AF XY: 0.420 AC XY: 31185 AN XY: 74266

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.619

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.423

Alfa AF: 0.438 Hom.: 3472

Bravo AF: 0.398

Asia WGS AF: 0.481 AC: 1673 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.52

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: rs1319677; hg19: chr9-93565999;