Variant 1-101239021-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001400.5(S1PR1):c.37C>G(p.Arg13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,614,166 control chromosomes in the GnomAD database, including 341 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.014 ( 21 hom., cov: 32)

Exomes 𝑓: 0.019 ( 320 hom. )

Consequence

S1PR1
NM_001400.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

S1PR1 (HGNC:3165): (sphingosine-1-phosphate receptor 1) The protein encoded by this gene is structurally similar to G protein-coupled receptors and is highly expressed in endothelial cells. It binds the ligand sphingosine-1-phosphate with high affinity and high specificity, and suggested to be involved in the processes that regulate the differentiation of endothelial cells. Activation of this receptor induces cell-cell adhesion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

S1PR1 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=0.0029692352).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0145 (2206/152378) while in subpopulation NFE AF= 0.0215 (1465/68040). AF 95% confidence interval is 0.0206. There are 21 homozygotes in gnomad4. There are 1099 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2206 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S1PR1	NM_001400.5 link	c.37C>G	p.Arg13Gly	missense_variant	2/2	ENST00000305352.7	NP_001391.2	P21453

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7 link	c.37C>G	p.Arg13Gly	missense_variant	2/2	1	NM_001400.5	ENSP00000305416.6		P21453

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2206

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00981

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0371

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0139

AC:

3503

AN:

251198

Hom.:

AF XY:

0.0138

AC XY:

1877

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00573

Gnomad ASJ exome

AF:

0.00537

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.0358

Gnomad NFE exome

AF:

0.0199

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0186

AC:

27178

AN:

1461788

Hom.:

320

Cov.:

AF XY:

0.0182

AC XY:

13220

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00239

Gnomad4 AMR exome

AF:

0.00651

Gnomad4 ASJ exome

AF:

0.00586

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00224

Gnomad4 FIN exome

AF:

0.0367

Gnomad4 NFE exome

AF:

0.0211

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

AF:

0.0145

AC:

2206

AN:

152378

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1099

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.00980

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0371

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0170

Hom.:

Bravo

AF:

0.0115

TwinsUK

AF:

0.0248

AC:

ALSPAC

AF:

0.0200

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0179

AC:

154

ExAC

AF:

0.0138

AC:

1680

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0184

EpiControl

AF:

0.0180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.040

.;T;T;T;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.74

T;.;.;.;T

MetaRNN

Benign

0.0030

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.75

.;N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.44

.;N;.;.;.

REVEL

Benign

0.19

Sift

Benign

0.14

.;T;.;.;.

Sift4G

Benign

0.40

.;T;.;.;.

Polyphen

0.029

.;B;B;B;B

Vest4

0.028

MPC

1.3

ClinPred

0.0047

GERP RS

5.0

Varity_R

0.13

gMVP

0.91

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