Genetic Variant NM_001400.5:c.44C>G (chr1-101239028-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001400.5(S1PR1):c.44C>G(p.Ser15Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S15L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

S1PR1
NM_001400.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.292

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1421504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S1PR1	NM_001400.5	MANE Select	c.44C>G	p.Ser15Trp	missense	Exon 2 of 2	NP_001391.2
S1PR1	NM_001320730.2		c.44C>G	p.Ser15Trp	missense	Exon 2 of 2	NP_001307659.1	P21453
S1PR1	NR_174347.1		n.288C>G		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S1PR1	ENST00000305352.7	TSL:1 MANE Select	c.44C>G	p.Ser15Trp	missense	Exon 2 of 2	ENSP00000305416.6	P21453
S1PR1	ENST00000475289.2	TSL:3	c.44C>G	p.Ser15Trp	missense	Exon 2 of 2	ENSP00000498038.1	P21453
S1PR1	ENST00000648480.1		c.44C>G	p.Ser15Trp	missense	Exon 2 of 2	ENSP00000497478.1	P21453

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251352

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111978

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.31

CADD

Benign

7.8

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.13

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.78

M_CAP

Benign

0.058

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

PhyloP100

0.29

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.4

REVEL

Benign

0.18

Sift

Uncertain

0.0080

Sift4G

Benign

0.12

Polyphen

0.77

Vest4

0.29

MutPred

0.34

Loss of disorder (P = 0.0037)

MVP

0.35

MPC

2.0

ClinPred

0.29

GERP RS

2.5

Varity_R

0.063

gMVP

0.89

Mutation Taster

=92/8

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over