Variant 17-76387026-CG-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001142601.2(SPHK1):c.596delG(p.Arg199fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.00286 in 1,613,618 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 12 hom. )

Consequence

SPHK1
NM_001142601.2 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.36

Variant links:

Genes affected

SPHK1 (HGNC:11240): (sphingosine kinase 1) The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Phosphorylation of this protein alters its catalytic activity and promotes its translocation to the plasma membrane. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]

SPHK1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 17-76387026-CG-C is Benign according to our data. Variant chr17-76387026-CG-C is described in ClinVar as [Likely_benign]. Clinvar id is 789900.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 290 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPHK1	NM_001142601.2 link	c.596delG	p.Arg199fs	frameshift_variant	6/6	ENST00000592299.6	NP_001136073.1	Q9NYA1-1Q53ZR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPHK1	ENST00000592299.6 link	c.596delG	p.Arg199fs	frameshift_variant	6/6	1	NM_001142601.2	ENSP00000465726.2		Q9NYA1-1

Frequencies

GnomAD3 genomes

AF:

0.00191

AC:

290

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00219

AC:

549

AN:

250850

Hom.:

AF XY:

0.00252

AC XY:

342

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00395

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00296

AC:

4320

AN:

1461320

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

2201

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.00123

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00366

Gnomad4 FIN exome

AF:

0.00147

Gnomad4 NFE exome

AF:

0.00331

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.00190

AC:

290

AN:

152298

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000547

Hom.:

Bravo

AF:

0.00190

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00338

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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