Genetic Variant S1PR1:c.-164+841C>G (chr1-101236367-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000945456.1(S1PR1):c.-164+841C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,190 control chromosomes in the GnomAD database, including 10,822 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10801 hom., cov: 30)

Exomes 𝑓: 0.32 ( 21 hom. )

Consequence

S1PR1
ENST00000945456.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.99

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

new If you want to explore the variant's impact on the transcript ENST00000945456.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.69).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000945456.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR1-DT	NR_104626.1		n.162G>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
S1PR1	ENST00000945456.1		c.-164+841C>G	intron	N/A	ENSP00000615515.1
S1PR1-DT	ENST00000432195.3	TSL:2	n.284G>C	non_coding_transcript_exon	Exon 1 of 2
S1PR1-DT	ENST00000686331.3		n.449G>C	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56103

AN:

151686

Hom.:

10797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.362

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.414

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.355

GnomAD4 exome

AF:

0.318

AC:

122

AN:

384

Hom.:

Cov.:

AF XY:

0.316

AC XY:

AN XY:

294

show subpopulations

African (AFR)

AF:

0.200

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.0556

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.438

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.340

AC:

106

AN:

312

Other (OTH)

AF:

0.0833

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.370

AC:

56122

AN:

151806

Hom.:

10801

Cov.:

AF XY:

0.366

AC XY:

27160

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.418

AC:

17291

AN:

41360

American (AMR)

AF:

0.299

AC:

4566

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1142

AN:

3472

East Asian (EAS)

AF:

0.117

AC:

605

AN:

5152

South Asian (SAS)

AF:

0.415

AC:

1999

AN:

4816

European-Finnish (FIN)

AF:

0.373

AC:

3927

AN:

10538

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.374

AC:

25427

AN:

67902

Other (OTH)

AF:

0.351

AC:

741

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1768

3537

5305

7074

8842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<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:

0.260

Hom.:

649

Bravo

AF:

0.361

Asia WGS

AF:

0.290

AC:

1009

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.6

(source)

DANN

Benign

0.84

PhyloP100

-4.0

PromoterAI

-0.045

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over