rs290254

Variant names:

• chr9-90889603-G-C
• rs290254
• NM_003177.7:c.1835+976G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003177.7(SYK):​c.1835+976G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,076 control chromosomes in the GnomAD database, including 26,119 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 0.58 (26119 hom., cov: 33)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 4 publications found

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]

SYK Gene-Disease associations (from GenCC):

• immunodeficiency 82 with systemic inflammation

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.1835+976G>C		intron_variant	Intron 13 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.1835+976G>C		intron_variant	Intron 13 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.1835+976G>C		intron_variant	Intron 13 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.1766+976G>C		intron_variant	Intron 12 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.1766+976G>C		intron_variant	Intron 12 of 12	1		ENSP00000364904.4

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88722 AN: 151958 Hom.: 26094 Cov.: 33

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.584 AC: 88780 AN: 152076 Hom.: 26119 Cov.: 33 AF XY: 0.582 AC XY: 43292 AN XY: 74334

African (AFR) AF: 0.600 AC: 24889 AN: 41466

American (AMR) AF: 0.481 AC: 7363 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2288 AN: 3468

East Asian (EAS) AF: 0.585 AC: 3027 AN: 5178

South Asian (SAS) AF: 0.580 AC: 2793 AN: 4814

European-Finnish (FIN) AF: 0.618 AC: 6526 AN: 10560

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39947 AN: 67984

Other (OTH) AF: 0.607 AC: 1280 AN: 2110

Alfa AF: 0.588 Hom.: 3292

Bravo AF: 0.573

Asia WGS AF: 0.561 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.14
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs290254; hg19: chr9-93651885;