rs7855964

Variant names:

• chr9-90843821-G-A
• rs7855964
• NM_003177.7:c.-41-37G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-90843821-G-A
• chr9-90843821-G-C
• chr9-90843821-G-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.-41-37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 1,382,802 control chromosomes in the GnomAD database, including 52,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7874 hom., cov: 32)
  • Exomes 𝑓: 0.26 (44161 hom.)
• Consequence: SYK NM_003177.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.834
• Publications: 8 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), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-90843821-G-A is Benign according to our data. Variant chr9-90843821-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 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.-41-37G>A		intron	N/A	NP_003168.2
	SYK	NM_001174167.3		c.-41-37G>A		intron	N/A	NP_001167638.1	P43405-1
	SYK	NM_001135052.4		c.-41-37G>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.-41-37G>A		intron	N/A	ENSP00000364907.4	P43405-1
	SYK	ENST00000375746.1	TSL:1	c.-41-37G>A		intron	N/A	ENSP00000364898.1	P43405-1
	SYK	ENST00000375747.5	TSL:1	c.-41-37G>A		intron	N/A	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46427 AN: 151888 Hom.: 7865 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.309

GnomAD4 exome AF: 0.261 AC: 321420 AN: 1230794 Hom.: 44161 Cov.: 23 AF XY: 0.261 AC XY: 155011 AN XY: 594188

African (AFR) AF: 0.432 AC: 11375 AN: 26302

American (AMR) AF: 0.376 AC: 5610 AN: 14924

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 5311 AN: 17922

East Asian (EAS) AF: 0.0234 AC: 748 AN: 31924

South Asian (SAS) AF: 0.223 AC: 12388 AN: 55446

European-Finnish (FIN) AF: 0.170 AC: 5336 AN: 31426

Middle Eastern (MID) AF: 0.339 AC: 1274 AN: 3762

European-Non Finnish (NFE) AF: 0.266 AC: 265871 AN: 997802

Other (OTH) AF: 0.263 AC: 13507 AN: 51286

GnomAD4 genome AF: 0.306 AC: 46464 AN: 152008 Hom.: 7874 Cov.: 32 AF XY: 0.299 AC XY: 22225 AN XY: 74314

African (AFR) AF: 0.418 AC: 17329 AN: 41422

American (AMR) AF: 0.365 AC: 5573 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3468

East Asian (EAS) AF: 0.0322 AC: 166 AN: 5158

South Asian (SAS) AF: 0.225 AC: 1083 AN: 4816

European-Finnish (FIN) AF: 0.155 AC: 1637 AN: 10588

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18475 AN: 67952

Other (OTH) AF: 0.308 AC: 652 AN: 2114

Alfa AF: 0.282 Hom.: 10671

Bravo AF: 0.327

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

ClinVar submissions

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	1.0
DANN	Benign	0.62
PhyloP100		-0.83
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: rs7855964; hg19: chr9-93606103;