Genetic Variant S1PR1:c.-164+399T>C (chr1-101235925-T-C) – 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+399T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,808 control chromosomes in the GnomAD database, including 9,293 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 0.34 ( 9293 hom., cov: 30)

Exomes 𝑓: 0.28 ( 0 hom. )

Consequence

S1PR1
ENST00000945456.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

2 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:

ENSG00000306729 (HGNC:):

ENSG00000306729 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=-0.82).

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.205-44A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
S1PR1	ENST00000945456.1	c.-164+399T>C	intron	N/A	ENSP00000615515.1
S1PR1-DT	ENST00000686331.3	n.891A>G	non_coding_transcript_exon	Exon 1 of 1
S1PR1-DT	ENST00000820226.1	n.700A>G	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51812

AN:

151672

Hom.:

9286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.318

GnomAD4 exome

AF:

0.278

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.342

AC:

51839

AN:

151790

Hom.:

9293

Cov.:

AF XY:

0.339

AC XY:

25181

AN XY:

74186

show subpopulations

African (AFR)

AF:

0.418

AC:

17272

AN:

41326

American (AMR)

AF:

0.263

AC:

4015

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.262

AC:

908

AN:

3472

East Asian (EAS)

AF:

0.127

AC:

655

AN:

5168

South Asian (SAS)

AF:

0.416

AC:

2001

AN:

4812

European-Finnish (FIN)

AF:

0.346

AC:

3639

AN:

10528

Middle Eastern (MID)

AF:

0.286

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.328

AC:

22285

AN:

67914

Other (OTH)

AF:

0.314

AC:

662

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1690

3381

5071

6762

8452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.330

Hom.:

7834

Bravo

AF:

0.332

Asia WGS

AF:

0.288

AC:

1000

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.1

(source)

DANN

Benign

0.52

PhyloP100

0.23

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over