Variant rs2247856 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182965.3(SPHK1):c.88G>A(p.Ala30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,556,998 control chromosomes in the GnomAD database, including 148,100 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 10417 hom., cov: 33)

Exomes 𝑓: 0.43 ( 137683 hom. )

Consequence

SPHK1
NM_182965.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.181

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.532199E-5).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPHK1	NM_001142601.2 link	c.-171G>A		5_prime_UTR_variant	2/6	ENST00000592299.6	NP_001136073.1	Q9NYA1-1Q53ZR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPHK1	ENST00000592299 link	c.-171G>A		5_prime_UTR_variant	2/6	1	NM_001142601.2	ENSP00000465726.2		Q9NYA1-1

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

51121

AN:

152012

Hom.:

10425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0924

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.400

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.338

GnomAD3 exomes

AF:

0.399

AC:

66239

AN:

166032

Hom.:

14076

AF XY:

0.396

AC XY:

36478

AN XY:

92148

show subpopulations

Gnomad AFR exome

AF:

0.0808

Gnomad AMR exome

AF:

0.447

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.324

Gnomad FIN exome

AF:

0.454

Gnomad NFE exome

AF:

0.471

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.435

AC:

610761

AN:

1404868

Hom.:

137683

Cov.:

AF XY:

0.432

AC XY:

300168

AN XY:

695512

show subpopulations

Gnomad4 AFR exome

AF:

0.0786

Gnomad4 AMR exome

AF:

0.440

Gnomad4 ASJ exome

AF:

0.385

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.315

Gnomad4 FIN exome

AF:

0.446

Gnomad4 NFE exome

AF:

0.465

Gnomad4 OTH exome

AF:

0.404

GnomAD4 genome

AF:

0.336

AC:

51112

AN:

152130

Hom.:

10417

Cov.:

AF XY:

0.335

AC XY:

24904

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0922

Gnomad4 AMR

AF:

0.399

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.314

Gnomad4 FIN

AF:

0.447

Gnomad4 NFE

AF:

0.460

Gnomad4 OTH

AF:

0.338

Alfa

AF:

0.427

Hom.:

11032

Bravo

AF:

0.321

TwinsUK

AF:

0.472

AC:

1750

ALSPAC

AF:

0.473

AC:

1822

ESP6500AA

AF:

0.0822

AC:

269

ESP6500EA

AF:

0.411

AC:

2929

ExAC

AF:

0.350

AC:

39119

Asia WGS

AF:

0.281

AC:

978

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.38

MetaRNN

Benign

0.000065

MetaSVM

Benign

-0.91

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.58

REVEL

Benign

0.013

Sift

Benign

0.034

Sift4G

Uncertain

0.044

Polyphen

0.025

Vest4

0.031

MPC

0.29

ClinPred

0.0042

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over