Genetic Variant SYK:c.1836-49A>T (chr9-90895479-A-T) – 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.1836-49A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,602,760 control chromosomes in the GnomAD database, including 251,630 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.59 ( 27444 hom., cov: 32)

Exomes 𝑓: 0.55 ( 224186 hom. )

Consequence

SYK
NM_003177.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.245

Publications

13 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 9-90895479-A-T is Benign according to our data. Variant chr9-90895479-A-T is described in ClinVar as Benign. ClinVar VariationId is 2687942.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.715 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.1836-49A>T	intron	N/A	NP_003168.2
SYK	NM_001174167.3		c.1836-49A>T	intron	N/A	NP_001167638.1	P43405-1
SYK	NM_001135052.4		c.1767-49A>T	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.1836-49A>T	intron	N/A	ENSP00000364907.4	P43405-1
SYK	ENST00000375746.1	TSL:1	c.1836-49A>T	intron	N/A	ENSP00000364898.1	P43405-1
SYK	ENST00000375747.5	TSL:1	c.1767-49A>T	intron	N/A	ENSP00000364899.1	P43405-2

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90211

AN:

151944

Hom.:

27411

Cov.:

show subpopulations

Gnomad AFR

AF:

0.722

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.584

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.407

Gnomad NFE

AF:

0.540

Gnomad OTH

AF:

0.540

GnomAD2 exomes

AF:

0.564

AC:

139040

AN:

246730

AF XY:

0.558

show subpopulations

Gnomad AFR exome

AF:

0.723

Gnomad AMR exome

AF:

0.631

Gnomad ASJ exome

AF:

0.481

Gnomad EAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.589

Gnomad NFE exome

AF:

0.540

Gnomad OTH exome

AF:

0.524

GnomAD4 exome

AF:

0.553

AC:

802672

AN:

1450694

Hom.:

224186

Cov.:

AF XY:

0.553

AC XY:

399581

AN XY:

722202

show subpopulations

African (AFR)

AF:

0.727

AC:

24210

AN:

33300

American (AMR)

AF:

0.630

AC:

28140

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.487

AC:

12676

AN:

26028

East Asian (EAS)

AF:

0.397

AC:

15742

AN:

39608

South Asian (SAS)

AF:

0.601

AC:

51682

AN:

85932

European-Finnish (FIN)

AF:

0.582

AC:

30145

AN:

51824

Middle Eastern (MID)

AF:

0.437

AC:

2504

AN:

5734

European-Non Finnish (NFE)

AF:

0.548

AC:

605026

AN:

1103632

Other (OTH)

AF:

0.542

AC:

32547

AN:

59996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

17959

35917

53876

71834

89793

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17202

34404

51606

68808

86010

<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:

0.594

AC:

90294

AN:

152066

Hom.:

27444

Cov.:

AF XY:

0.593

AC XY:

44071

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.722

AC:

29940

AN:

41492

American (AMR)

AF:

0.585

AC:

8938

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

1666

AN:

3466

East Asian (EAS)

AF:

0.400

AC:

2068

AN:

5172

South Asian (SAS)

AF:

0.598

AC:

2879

AN:

4816

European-Finnish (FIN)

AF:

0.602

AC:

6366

AN:

10572

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.540

AC:

36694

AN:

67950

Other (OTH)

AF:

0.536

AC:

1130

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1847

3695

5542

7390

9237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.463

Hom.:

2207

Bravo

AF:

0.596

Asia WGS

AF:

0.501

AC:

1744

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

1.3

(source)

DANN

Benign

0.55

PhyloP100

-0.24

Mutation Taster

=6/94

disease causing

(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