Genetic Variant S1PR1:c.-358delG (chr1-101236991-AG-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_ModerateBA1

The NM_001320730.2(S1PR1):c.-164+1delG variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 152,120 control chromosomes in the GnomAD database, including 1,148 homozygotes. 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 0.090 ( 1148 hom., cov: 29)

Exomes 𝑓: 0.041 ( 0 hom. )

Consequence

S1PR1
NM_001320730.2 splice_donor, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.246

Publications

6 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: Likely_benign. The variant received -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.08093995 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320730.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
S1PR1	NM_001320730.2	c.-164+1delG	splice_donor intron	N/A	NP_001307659.1	P21453
S1PR1	NR_174348.1	n.93+1delG	splice_donor intron	N/A
S1PR1	NR_174350.1	n.93+1delG	splice_donor intron	N/A

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
S1PR1	ENST00000876129.1	c.-358delG	5_prime_UTR	Exon 1 of 3	ENSP00000546188.1
S1PR1	ENST00000945456.1	c.-164+1466delG	intron	N/A	ENSP00000615515.1
S1PR1	ENST00000945457.1	c.-251+1delG	splice_donor intron	N/A	ENSP00000615516.1

Frequencies

GnomAD3 genomes

AF:

0.0897

AC:

13614

AN:

151852

Hom.:

1147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.0553

Gnomad ASJ

AF:

0.0542

Gnomad EAS

AF:

0.0574

Gnomad SAS

AF:

0.0857

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0882

GnomAD4 exome

AF:

0.0405

AC:

AN:

148

Hom.:

Cov.:

AF XY:

0.0500

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.0513

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0200

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0896

AC:

13621

AN:

151972

Hom.:

1148

Cov.:

AF XY:

0.0879

AC XY:

6530

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.218

AC:

9014

AN:

41414

American (AMR)

AF:

0.0552

AC:

843

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0542

AC:

188

AN:

3470

East Asian (EAS)

AF:

0.0573

AC:

296

AN:

5164

South Asian (SAS)

AF:

0.0858

AC:

412

AN:

4804

European-Finnish (FIN)

AF:

0.0143

AC:

151

AN:

10572

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0364

AC:

2474

AN:

67964

Other (OTH)

AF:

0.0868

AC:

183

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

572

1144

1717

2289

2861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<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:

0.0115

Hom.:

Bravo

AF:

0.0971

Asia WGS

AF:

0.0870

AC:

304

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.25

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over