Genetic Variant S1PR1:n.2830T>C (chr1-101241570-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 XR_007095678.1(S1PR1):n.2830T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 165,572 control chromosomes in the GnomAD database, including 2,430 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 0.14 ( 2351 hom., cov: 32)

Exomes 𝑓: 0.10 ( 79 hom. )

Consequence

S1PR1
XR_007095678.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.590

Publications

4 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000305352.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
S1PR1	NR_174345.1	n.82-119T>C	intron	N/A
S1PR1	NR_174346.1	n.82-458T>C	intron	N/A
S1PR1	NR_174347.1	n.1796-458T>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
S1PR1	ENST00000561748.2	TSL:6	n.202-119T>C	intron	N/A
S1PR1	ENST00000305352.7	TSL:1 MANE Select	c.*1437T>C	downstream_gene	N/A	ENSP00000305416.6	P21453
S1PR1	ENST00000475289.2	TSL:3	c.*1437T>C	downstream_gene	N/A	ENSP00000498038.1	P21453

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21064

AN:

152008

Hom.:

2335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.265

Gnomad ASJ

AF:

0.0494

Gnomad EAS

AF:

0.0880

Gnomad SAS

AF:

0.0507

Gnomad FIN

AF:

0.0993

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0522

Gnomad OTH

AF:

0.115

GnomAD4 exome

AF:

0.102

AC:

1375

AN:

13446

Hom.:

AF XY:

0.103

AC XY:

659

AN XY:

6414

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0845

AC:

AN:

142

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.103

AC:

1350

AN:

13138

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0789

AC:

AN:

Other (OTH)

AF:

0.0625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

118

178

237

296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.139

AC:

21116

AN:

152126

Hom.:

2351

Cov.:

AF XY:

0.142

AC XY:

10529

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.271

AC:

11247

AN:

41444

American (AMR)

AF:

0.266

AC:

4068

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0494

AC:

171

AN:

3464

East Asian (EAS)

AF:

0.0878

AC:

455

AN:

5182

South Asian (SAS)

AF:

0.0507

AC:

245

AN:

4830

European-Finnish (FIN)

AF:

0.0993

AC:

1052

AN:

10590

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0522

AC:

3549

AN:

68006

Other (OTH)

AF:

0.114

AC:

240

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

817

1634

2451

3268

4085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.0935

Hom.:

299

Bravo

AF:

0.162

Asia WGS

AF:

0.0860

AC:

295

AN:

3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.79

(source)

DANN

Benign

0.56

PhyloP100

0.59

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over