chr9-90872131-G-A

Position:

• chr9-90872131-G-A

Variant summary

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

The NM_003177.7(SYK):​c.916-2073G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,076 control chromosomes in the GnomAD database, including 4,511 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 0.22 (4511 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.916-2073G>A		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.916-2073G>A		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375746.1	c.916-2073G>A		intron_variant		1		P1
SYK	ENST00000375747.5	c.847-2073G>A		intron_variant		1
SYK	ENST00000375751.8	c.847-2073G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34144 AN: 151958 Hom.: 4506 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.225 AC: 34167 AN: 152076 Hom.: 4511 Cov.: 33 AF XY: 0.232 AC XY: 17212 AN XY: 74350

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.240

Alfa AF: 0.216 Hom.: 4918

Bravo AF: 0.217

Asia WGS AF: 0.498 AC: 1729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.0020
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs290229; hg19: chr9-93634413; COSMIC: COSV65326234;