dbSNP rs290227: SYK:c.1003+91G>A (chr9-90874382-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003177.7(SYK):c.1003+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,280,998 control chromosomes in the GnomAD database, including 58,775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 7513 hom., cov: 32)

Exomes 𝑓: 0.29 ( 51262 hom. )

Consequence

SYK
NM_003177.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.329

Publications

22 publications found

Variant links:

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

SYK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-90874382-G-A is Benign according to our data. Variant chr9-90874382-G-A is described in ClinVar as Benign. ClinVar VariationId is 2688172.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.583 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYK	NM_003177.7	MANE Select	c.1003+91G>A	intron	N/A	NP_003168.2
SYK	NM_001174167.3		c.1003+91G>A	intron	N/A	NP_001167638.1	P43405-1
SYK	NM_001135052.4		c.934+91G>A	intron	N/A	NP_001128524.1	P43405-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SYK	ENST00000375754.9	TSL:1 MANE Select	c.1003+91G>A	intron	N/A	ENSP00000364907.4	P43405-1
SYK	ENST00000375746.1	TSL:1	c.1003+91G>A	intron	N/A	ENSP00000364898.1	P43405-1
SYK	ENST00000375747.5	TSL:1	c.934+91G>A	intron	N/A	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45863

AN:

151846

Hom.:

7503

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.302

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.237

Gnomad EAS

AF:

0.601

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.280

Gnomad NFE

AF:

0.246

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.287

AC:

324445

AN:

1129036

Hom.:

51262

AF XY:

0.294

AC XY:

167760

AN XY:

570486

show subpopulations

African (AFR)

AF:

0.356

AC:

9594

AN:

26958

American (AMR)

AF:

0.243

AC:

9785

AN:

40324

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

5632

AN:

23604

East Asian (EAS)

AF:

0.604

AC:

22543

AN:

37328

South Asian (SAS)

AF:

0.483

AC:

37510

AN:

77660

European-Finnish (FIN)

AF:

0.330

AC:

16233

AN:

49240

Middle Eastern (MID)

AF:

0.277

AC:

1410

AN:

5096

European-Non Finnish (NFE)

AF:

0.252

AC:

206839

AN:

819468

Other (OTH)

AF:

0.302

AC:

14899

AN:

49358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

11189

22377

33566

44754

55943

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6596

13192

19788

26384

32980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.302

AC:

45920

AN:

151962

Hom.:

7513

Cov.:

AF XY:

0.311

AC XY:

23059

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.351

AC:

14527

AN:

41442

American (AMR)

AF:

0.247

AC:

3770

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

820

AN:

3466

East Asian (EAS)

AF:

0.600

AC:

3083

AN:

5136

South Asian (SAS)

AF:

0.507

AC:

2439

AN:

4808

European-Finnish (FIN)

AF:

0.345

AC:

3630

AN:

10534

Middle Eastern (MID)

AF:

0.274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.246

AC:

16723

AN:

67978

Other (OTH)

AF:

0.271

AC:

573

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1602

3204

4807

6409

8011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.265

Hom.:

21820

Bravo

AF:

0.297

Asia WGS

AF:

0.526

AC:

1827

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.4

(source)

DANN

Benign

0.66

PhyloP100

-0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over