rs1760124

Variant names:

• chr9-90867065-G-A
• rs1760124
• NM_003177.7:c.847-66G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003177.7(SYK):​c.847-66G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 1,583,454 control chromosomes in the GnomAD database, including 513,383 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.85 (54736 hom., cov: 31)
  • Exomes 𝑓: 0.80 (458647 hom.)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.67
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-90867065-G-A is Benign according to our data. Variant chr9-90867065-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003177.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	NM_003177.7	MANE Select	c.847-66G>A		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.847-66G>A		intron	N/A	NP_001167638.1	P43405-1
	SYK	NM_001135052.4		c.846+1968G>A		intron	N/A	NP_001128524.1	P43405-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYK	ENST00000375754.9	TSL:1 MANE Select	c.847-66G>A		intron	N/A	ENSP00000364907.4	P43405-1
	SYK	ENST00000375746.1	TSL:1	c.847-66G>A		intron	N/A	ENSP00000364898.1	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.846+1968G>A		intron	N/A	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128456 AN: 152030 Hom.: 54677 Cov.: 31

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.857

GnomAD4 exome AF: 0.799 AC: 1144197 AN: 1431306 Hom.: 458647 AF XY: 0.800 AC XY: 571313 AN XY: 713874

African (AFR) AF: 0.941 AC: 30947 AN: 32888

American (AMR) AF: 0.863 AC: 38544 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 22183 AN: 25898

East Asian (EAS) AF: 0.943 AC: 37261 AN: 39516

South Asian (SAS) AF: 0.844 AC: 72241 AN: 85548

European-Finnish (FIN) AF: 0.811 AC: 42900 AN: 52912

Middle Eastern (MID) AF: 0.876 AC: 4044 AN: 4618

European-Non Finnish (NFE) AF: 0.780 AC: 847400 AN: 1086032

Other (OTH) AF: 0.822 AC: 48677 AN: 59252

GnomAD4 genome AF: 0.845 AC: 128574 AN: 152148 Hom.: 54736 Cov.: 31 AF XY: 0.849 AC XY: 63129 AN XY: 74374

African (AFR) AF: 0.934 AC: 38756 AN: 41510

American (AMR) AF: 0.863 AC: 13192 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2979 AN: 3470

East Asian (EAS) AF: 0.955 AC: 4948 AN: 5180

South Asian (SAS) AF: 0.855 AC: 4119 AN: 4818

European-Finnish (FIN) AF: 0.810 AC: 8561 AN: 10568

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53088 AN: 68002

Other (OTH) AF: 0.858 AC: 1810 AN: 2110

Alfa AF: 0.811 Hom.: 31399

Bravo AF: 0.854

Asia WGS AF: 0.919 AC: 3194 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0060
DANN	Benign	0.83
PhyloP100		-2.7
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: rs1760124; hg19: chr9-93629347;