1-101239414-A-G

Position:

• chr1-101239414-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001400.5(S1PR1):​c.430A>G​(p.Ile144Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: S1PR1 NM_001400.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28605023).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S1PR1	NM_001400.5	c.430A>G	p.Ile144Val	missense_variant	2/2	ENST00000305352.7	NP_001391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7	c.430A>G	p.Ile144Val	missense_variant	2/2	1	NM_001400.5	ENSP00000305416.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2023

The c.430A>G (p.I144V) alteration is located in exon 2 (coding exon 1) of the S1PR1 gene. This alteration results from a A to G substitution at nucleotide position 430, causing the isoleucine (I) at amino acid position 144 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.058	.;T;T;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.61	T;.;.;.;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.29	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	.;L;L;L;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.19	.;N;.;.;.
REVEL	Benign	0.056
Sift	Benign	0.57	.;T;.;.;.
Sift4G	Benign	0.69	.;T;.;.;.
Polyphen		0.0070	.;B;B;B;B
Vest4		0.26
MVP		0.34
MPC		0.92
ClinPred		0.93	D
GERP RS		4.5
Varity_R		0.062
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-101704970; COSMIC: COSV59514750; COSMIC: COSV59514750;