Variant 9-90877564-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003177.7(SYK):c.1182-7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,613,642 control chromosomes in the GnomAD database, including 43,059 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 4164 hom., cov: 33)

Exomes 𝑓: 0.22 ( 38895 hom. )

Consequence

SYK
NM_003177.7 splice_region, intron

Scores

Splicing: ADA: 0.00007411

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.332

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-90877564-C-G is Benign according to our data. Variant chr9-90877564-C-G is described in ClinVar as [Benign]. Clinvar id is 2688259.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYK	NM_003177.7 link	c.1182-7C>G		splice_region_variant, intron_variant	Intron 9 of 13	ENST00000375754.9	NP_003168.2	P43405-1A0A024R244

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SYK	ENST00000375754.9 link	c.1182-7C>G	splice_region_variant, intron_variant	Intron 9 of 13	1	NM_003177.7	ENSP00000364907.4	P43405-1
SYK	ENST00000375746.1 link	c.1182-7C>G	splice_region_variant, intron_variant	Intron 9 of 13	1		ENSP00000364898.1	P43405-1
SYK	ENST00000375747.5 link	c.1113-7C>G	splice_region_variant, intron_variant	Intron 8 of 12	1		ENSP00000364899.1	P43405-2
SYK	ENST00000375751.8 link	c.1113-7C>G	splice_region_variant, intron_variant	Intron 8 of 12	1		ENSP00000364904.4	P43405-2

Frequencies

GnomAD3 genomes

AF:

0.222

AC:

33699

AN:

152034

Hom.:

4160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.285

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.539

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.210

GnomAD3 exomes

AF:

0.247

AC:

62130

AN:

251034

Hom.:

8937

AF XY:

0.249

AC XY:

33843

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.228

Gnomad AMR exome

AF:

0.184

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.549

Gnomad SAS exome

AF:

0.339

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.199

Gnomad OTH exome

AF:

0.227

GnomAD4 exome

AF:

0.222

AC:

323794

AN:

1461490

Hom.:

38895

Cov.:

AF XY:

0.224

AC XY:

163057

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.533

Gnomad4 SAS exome

AF:

0.334

Gnomad4 FIN exome

AF:

0.255

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.235

GnomAD4 genome

AF:

0.222

AC:

33733

AN:

152152

Hom.:

4164

Cov.:

AF XY:

0.228

AC XY:

16969

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.181

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.539

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.132

Hom.:

316

Bravo

AF:

0.222

EpiCase

AF:

0.195

EpiControl

AF:

0.198

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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 29% of patients studied by a panel of primary immunodeficiencies. Number of patients: 28. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.3

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000074

dbscSNV1_RF

Benign

0.0040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over