rs1333633

Positions:

• chr9-90805290-G-A
• chr9-90805290-G-C
• chr9-90805290-G-T

Variant summary

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

The NM_003177.7(SYK):​c.-42+3397G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,980 control chromosomes in the GnomAD database, including 23,291 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 0.55 (23291 hom., cov: 32)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYK	NM_003177.7	c.-42+3397G>A		intron_variant		ENST00000375754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYK	ENST00000375754.9	c.-42+3397G>A		intron_variant		1	NM_003177.7	P1
SYK	ENST00000375747.5	c.-42+3285G>A		intron_variant		1
SYK	ENST00000375751.8	c.-42+3397G>A		intron_variant		1
SYK	ENST00000476708.1	n.78+3251G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82908 AN: 151862 Hom.: 23277 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.546 AC: 82963 AN: 151980 Hom.: 23291 Cov.: 32 AF XY: 0.555 AC XY: 41263 AN XY: 74286

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.566

Alfa AF: 0.563 Hom.: 32381

Bravo AF: 0.542

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.46

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: rs1333633; hg19: chr9-93567572;