dbSNP rs4987248: S1PR1:c.-165G>C (chr1-101236990-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001320730.2(S1PR1):c.-165G>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 148,956 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.069 ( 589 hom., cov: 30)

Exomes 𝑓: 0.048 ( 0 hom. )

Consequence

S1PR1
NM_001320730.2 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

Publications

5 publications found

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:

S1PR1-DT (HGNC:55842): (S1PR1 divergent transcript)

S1PR1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR1	NM_001400.5 link	c.-273G>C		upstream_gene_variant		ENST00000305352.7	NP_001391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7 link	c.-273G>C		upstream_gene_variant		1	NM_001400.5	ENSP00000305416.6

Frequencies

GnomAD3 genomes

AF:

0.0695

AC:

10339

AN:

148694

Hom.:

590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0680

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.0496

Gnomad FIN

AF:

0.0771

Gnomad MID

AF:

0.0548

Gnomad NFE

AF:

0.0542

Gnomad OTH

AF:

0.0761

GnomAD4 exome

AF:

0.0479

AC:

AN:

146

Hom.:

Cov.:

AF XY:

0.0600

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0405

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0577

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0695

AC:

10337

AN:

148810

Hom.:

589

Cov.:

AF XY:

0.0720

AC XY:

5232

AN XY:

72706

show subpopulations

African (AFR)

AF:

0.0678

AC:

2628

AN:

38766

American (AMR)

AF:

0.0496

AC:

752

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

456

AN:

3458

East Asian (EAS)

AF:

0.311

AC:

1587

AN:

5102

South Asian (SAS)

AF:

0.0494

AC:

232

AN:

4696

European-Finnish (FIN)

AF:

0.0771

AC:

814

AN:

10560

Middle Eastern (MID)

AF:

0.0590

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0542

AC:

3673

AN:

67810

Other (OTH)

AF:

0.0758

AC:

157

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

480

960

1440

1920

2400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0614

Hom.:

Bravo

AF:

0.0675

Asia WGS

AF:

0.153

AC:

526

AN:

3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.4

(source)

DANN

Benign

0.88

PhyloP100

-2.0

PromoterAI

-0.061

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over