chr9-90877564-C-A

Variant names:

• chr9-90877564-C-A
• rs290223
• NM_003177.7:c.1182-7C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003177.7(SYK):​c.1182-7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,613,860 control chromosomes in the GnomAD database, including 85 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 0.013 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (45 hom.)
• Consequence: SYK NM_003177.7 splice_region, intron
• Scores: Splicing: ADA: 0.00006384
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.332

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 9-90877564-C-A is Benign according to our data. Variant chr9-90877564-C-A is described in ClinVar as [Benign]. Clinvar id is 776432.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0126 (1917/152180) while in subpopulation AFR AF = 0.0427 (1775/41522). AF 95% confidence interval is 0.0411. There are 40 homozygotes in GnomAd4. There are 932 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 1917 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1913 AN: 152062 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00359 AC: 900 AN: 251034 AF XY: 0.00260

Gnomad AFR exome AF: 0.0438

Gnomad AMR exome AF: 0.00342

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000423

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00151 AC: 2208 AN: 1461680 Hom.: 45 Cov.: 33 AF XY: 0.00137 AC XY: 995 AN XY: 727142

Gnomad4 AFR exome AF: 0.0447 AC: 1495 AN: 33472

Gnomad4 AMR exome AF: 0.00443 AC: 198 AN: 44706

Gnomad4 ASJ exome AF: 0.000650 AC: 17 AN: 26136

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39692

Gnomad4 SAS exome AF: 0.000220 AC: 19 AN: 86222

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53360

Gnomad4 NFE exome AF: 0.000209 AC: 232 AN: 1111942

Gnomad4 Remaining exome AF: 0.00364 AC: 220 AN: 60382

GnomAD4 genome AF: 0.0126 AC: 1917 AN: 152180 Hom.: 40 Cov.: 33 AF XY: 0.0125 AC XY: 932 AN XY: 74380

Gnomad4 AFR AF: 0.0427 AC: 0.0427484 AN: 0.0427484

Gnomad4 AMR AF: 0.00562 AC: 0.00562312 AN: 0.00562312

Gnomad4 ASJ AF: 0.000865 AC: 0.000865052 AN: 0.000865052

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000414 AC: 0.000413907 AN: 0.000413907

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000309 AC: 0.000308787 AN: 0.000308787

Gnomad4 OTH AF: 0.0104 AC: 0.0104068 AN: 0.0104068

Alfa AF: 0.000688 Hom.: 316

EpiCase AF: 0.000436

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.41
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000064
dbscSNV1_RF	Benign	0.018
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

Other links and lift over

dbSNP: rs290223; hg19: chr9-93639846;