Variant rs346803 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000323374.8(SPHK1):c.100G>A(p.Ala34Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 1,559,412 control chromosomes in the GnomAD database, including 609,864 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 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 0.88 ( 58912 hom., cov: 33)

Exomes 𝑓: 0.88 ( 550952 hom. )

Consequence

SPHK1
ENST00000323374.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.765

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=9.704484E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPHK1	NM_001142601.2 linkuse as main transcript	c.-159G>A		5_prime_UTR_variant	2/6	ENST00000592299.6	NP_001136073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPHK1	ENST00000592299.6 linkuse as main transcript	c.-159G>A		5_prime_UTR_variant	2/6	1	NM_001142601.2	ENSP00000465726	P2	Q9NYA1-1

Frequencies

GnomAD3 genomes

AF:

0.879

AC:

133643

AN:

152124

Hom.:

58859

Cov.:

show subpopulations

Gnomad AFR

AF:

0.840

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.903

Gnomad ASJ

AF:

0.882

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.932

Gnomad FIN

AF:

0.917

Gnomad MID

AF:

0.902

Gnomad NFE

AF:

0.878

Gnomad OTH

AF:

0.883

GnomAD3 exomes

AF:

0.908

AC:

153505

AN:

169066

Hom.:

69827

AF XY:

0.907

AC XY:

84939

AN XY:

93674

show subpopulations

Gnomad AFR exome

AF:

0.838

Gnomad AMR exome

AF:

0.934

Gnomad ASJ exome

AF:

0.895

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.936

Gnomad FIN exome

AF:

0.924

Gnomad NFE exome

AF:

0.879

Gnomad OTH exome

AF:

0.904

GnomAD4 exome

AF:

0.884

AC:

1244521

AN:

1407170

Hom.:

550952

Cov.:

AF XY:

0.887

AC XY:

617795

AN XY:

696840

show subpopulations

Gnomad4 AFR exome

AF:

0.834

Gnomad4 AMR exome

AF:

0.929

Gnomad4 ASJ exome

AF:

0.888

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.934

Gnomad4 FIN exome

AF:

0.922

Gnomad4 NFE exome

AF:

0.875

Gnomad4 OTH exome

AF:

0.890

GnomAD4 genome

AF:

0.879

AC:

133752

AN:

152242

Hom.:

58912

Cov.:

AF XY:

0.881

AC XY:

65607

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.840

Gnomad4 AMR

AF:

0.904

Gnomad4 ASJ

AF:

0.882

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.932

Gnomad4 FIN

AF:

0.917

Gnomad4 NFE

AF:

0.878

Gnomad4 OTH

AF:

0.884

Alfa

AF:

0.878

Hom.:

41956

Bravo

AF:

0.874

TwinsUK

AF:

0.873

AC:

3238

ALSPAC

AF:

0.875

AC:

3372

ESP6500AA

AF:

0.887

AC:

2918

ESP6500EA

AF:

0.900

AC:

6390

ExAC

AF:

0.883

AC:

97024

Asia WGS

AF:

0.971

AC:

3374

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.0

DANN

Benign

0.87

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.24

MetaRNN

Benign

9.7e-7

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.39

REVEL

Benign

0.037

Sift

Benign

1.0

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.022

MPC

0.29

ClinPred

0.0043

GERP RS

-4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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