9-90865202-C-T

Variant names:

• chr9-90865202-C-T
• rs4744516
• NM_003177.7:c.846+105C>T

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.846+105C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,151,070 control chromosomes in the GnomAD database, including 103,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14690 hom., cov: 33)
  • Exomes 𝑓: 0.41 (89091 hom.)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.443
• Publications: 14 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=-0.84).
• BP6: Variant 9-90865202-C-T is Benign according to our data. Variant chr9-90865202-C-T is described in ClinVar as Benign. ClinVar VariationId is 2688027.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.523 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.846+105C>T		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.846+105C>T		intron	N/A	NP_001167638.1	P43405-1
	SYK	NM_001135052.4		c.846+105C>T		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.846+105C>T		intron	N/A	ENSP00000364907.4	P43405-1
	SYK	ENST00000375746.1	TSL:1	c.846+105C>T		intron	N/A	ENSP00000364898.1	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.846+105C>T		intron	N/A	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65865 AN: 152016 Hom.: 14683 Cov.: 33

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.414 AC: 413889 AN: 998938 Hom.: 89091 AF XY: 0.408 AC XY: 209752 AN XY: 514482

African (AFR) AF: 0.454 AC: 11104 AN: 24462

American (AMR) AF: 0.573 AC: 23734 AN: 41418

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 11313 AN: 22824

East Asian (EAS) AF: 0.191 AC: 7136 AN: 37318

South Asian (SAS) AF: 0.241 AC: 17895 AN: 74186

European-Finnish (FIN) AF: 0.355 AC: 17694 AN: 49904

Middle Eastern (MID) AF: 0.496 AC: 2414 AN: 4866

European-Non Finnish (NFE) AF: 0.435 AC: 303755 AN: 698614

Other (OTH) AF: 0.416 AC: 18844 AN: 45346

GnomAD4 genome AF: 0.433 AC: 65908 AN: 152132 Hom.: 14690 Cov.: 33 AF XY: 0.426 AC XY: 31657 AN XY: 74358

African (AFR) AF: 0.455 AC: 18890 AN: 41496

American (AMR) AF: 0.533 AC: 8156 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1717 AN: 3466

East Asian (EAS) AF: 0.215 AC: 1113 AN: 5186

South Asian (SAS) AF: 0.227 AC: 1095 AN: 4820

European-Finnish (FIN) AF: 0.337 AC: 3562 AN: 10568

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29720 AN: 67980

Other (OTH) AF: 0.474 AC: 1001 AN: 2112

Alfa AF: 0.436 Hom.: 26057

Bravo AF: 0.452

Asia WGS AF: 0.234 AC: 815 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	-0.84
CADD	Benign	5.9
DANN	Benign	0.76
PhyloP100		0.44
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: rs4744516; hg19: chr9-93627484; COSMIC: COSV65326864;