rs10761395

Positions:

• chr9-90880615-T-C

Variant summary

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

The NM_003177.7(SYK):​c.1581+1662T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,008 control chromosomes in the GnomAD database, including 7,758 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 0.31 (7758 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463

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 (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.1581+1662T>C		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.1581+1662T>C		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375746.1	c.1581+1662T>C		intron_variant		1		P1
SYK	ENST00000375747.5	c.1512+1662T>C		intron_variant		1
SYK	ENST00000375751.8	c.1512+1662T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46630 AN: 151890 Hom.: 7757 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.00444

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.307 AC: 46639 AN: 152008 Hom.: 7758 Cov.: 32 AF XY: 0.297 AC XY: 22089 AN XY: 74322

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.00445

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.338

Alfa AF: 0.321 Hom.: 16522

Bravo AF: 0.313

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.058
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10761395; hg19: chr9-93642897;