dbSNP rs3737578: S1PR1:c.-45T>C (chr1-101238940-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 NM_001400.5(S1PR1):c.-45T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 1,559,516 control chromosomes in the GnomAD database, including 5,193 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 0.084 ( 674 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4519 hom. )

Consequence

S1PR1
NM_001400.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Publications

12 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:

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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR1	NM_001400.5 link	c.-45T>C		5_prime_UTR_variant	Exon 2 of 2	ENST00000305352.7	NP_001391.2	P21453

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7 link	c.-45T>C		5_prime_UTR_variant	Exon 2 of 2	1	NM_001400.5	ENSP00000305416.6		P21453

Frequencies

GnomAD3 genomes

AF:

0.0838

AC:

12761

AN:

152214

Hom.:

675

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0888

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0615

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.0770

Gnomad FIN

AF:

0.0937

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.0920

GnomAD2 exomes

AF:

0.0935

AC:

18042

AN:

193050

AF XY:

0.0931

show subpopulations

Gnomad AFR exome

AF:

0.0874

Gnomad AMR exome

AF:

0.0633

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.0957

Gnomad NFE exome

AF:

0.0690

Gnomad OTH exome

AF:

0.0819

GnomAD4 exome

AF:

0.0728

AC:

102437

AN:

1407184

Hom.:

4519

Cov.:

AF XY:

0.0734

AC XY:

51053

AN XY:

695852

show subpopulations

African (AFR)

AF:

0.0865

AC:

2776

AN:

32076

American (AMR)

AF:

0.0614

AC:

2309

AN:

37602

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

2918

AN:

22920

East Asian (EAS)

AF:

0.231

AC:

9017

AN:

39014

South Asian (SAS)

AF:

0.0876

AC:

6826

AN:

77878

European-Finnish (FIN)

AF:

0.0919

AC:

4582

AN:

49842

Middle Eastern (MID)

AF:

0.116

AC:

576

AN:

4960

European-Non Finnish (NFE)

AF:

0.0630

AC:

68396

AN:

1084820

Other (OTH)

AF:

0.0867

AC:

5037

AN:

58072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

5151

10302

15452

20603

25754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2694

5388

8082

10776

13470

<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:

0.0837

AC:

12755

AN:

152332

Hom.:

674

Cov.:

AF XY:

0.0864

AC XY:

6439

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0885

AC:

3679

AN:

41582

American (AMR)

AF:

0.0615

AC:

941

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

418

AN:

3466

East Asian (EAS)

AF:

0.264

AC:

1368

AN:

5182

South Asian (SAS)

AF:

0.0764

AC:

369

AN:

4830

European-Finnish (FIN)

AF:

0.0937

AC:

995

AN:

10618

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0694

AC:

4724

AN:

68028

Other (OTH)

AF:

0.0905

AC:

191

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

603

1205

1808

2410

3013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.0752

Hom.:

889

Bravo

AF:

0.0823

Asia WGS

AF:

0.148

AC:

515

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

4.3

(source)

DANN

Benign

0.65

PhyloP100

-1.1

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