9-90867065-G-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7	c.847-66G>A		intron_variant	Intron 6 of 13	ENST00000375754.9	NP_003168.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYK	ENST00000375754.9	c.847-66G>A		intron_variant	Intron 6 of 13	1	NM_003177.7	ENSP00000364907.4
SYK	ENST00000375746.1	c.847-66G>A		intron_variant	Intron 6 of 13	1		ENSP00000364898.1
SYK	ENST00000375747.5	c.846+1968G>A		intron_variant	Intron 6 of 12	1		ENSP00000364899.1
SYK	ENST00000375751.8	c.846+1968G>A		intron_variant	Intron 6 of 12	1		ENSP00000364904.4

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

Gnomad4 AFR exome AF: 0.941

Gnomad4 AMR exome AF: 0.863

Gnomad4 ASJ exome AF: 0.857

Gnomad4 EAS exome AF: 0.943

Gnomad4 SAS exome AF: 0.844

Gnomad4 FIN exome AF: 0.811

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.822

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

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.855

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.858

Alfa AF: 0.809 Hom.: 20262

Bravo AF: 0.854

Asia WGS AF: 0.919 AC: 3194 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0060
DANN	Benign	0.83

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: rs1760124; hg19: chr9-93629347;