Variant 9-90895479-A-T 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.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

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=-0.83).

BP6

Variant 9-90895479-A-T is Benign according to our data. Variant chr9-90895479-A-T is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYK	NM_003177.7 link	c.1836-49A>T		intron_variant		ENST00000375754.9	NP_003168.2	P43405-1A0A024R244

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SYK	ENST00000375754.9 link	c.1836-49A>T	intron_variant	1	NM_003177.7	ENSP00000364907.4	P43405-1
SYK	ENST00000375746.1 link	c.1836-49A>T	intron_variant	1		ENSP00000364898.1	P43405-1
SYK	ENST00000375747.5 link	c.1767-49A>T	intron_variant	1		ENSP00000364899.1	P43405-2
SYK	ENST00000375751.8 link	c.1767-49A>T	intron_variant	1		ENSP00000364904.4	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

GnomAD3 exomes

AF:

0.564

AC:

139040

AN:

246730

Hom.:

39893

AF XY:

0.558

AC XY:

74660

AN XY:

133716

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 SAS exome

AF:

0.602

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

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.630

Gnomad4 ASJ exome

AF:

0.487

Gnomad4 EAS exome

AF:

0.397

Gnomad4 SAS exome

AF:

0.601

Gnomad4 FIN exome

AF:

0.582

Gnomad4 NFE exome

AF:

0.548

Gnomad4 OTH exome

AF:

0.542

GnomAD4 genome

AF:

0.594

AC:

90294

AN:

152066

Hom.:

27444

Cov.:

AF XY:

0.593

AC XY:

44071

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.722

Gnomad4 AMR

AF:

0.585

Gnomad4 ASJ

AF:

0.481

Gnomad4 EAS

AF:

0.400

Gnomad4 SAS

AF:

0.598

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.540

Gnomad4 OTH

AF:

0.536

Alfa

AF:

0.463

Hom.:

2207

Bravo

AF:

0.596

Asia WGS

AF:

0.501

AC:

1744

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 91% of patients studied by a panel of primary immunodeficiencies. Number of patients: 86. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.3

DANN

Benign

0.55

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

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