rs3765684

Positions:

• chr1-101237032-A-G
• chr1-101237032-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001400.5(S1PR1):​c.-231A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 152,292 control chromosomes in the GnomAD database, including 595 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 0.068 (595 hom., cov: 30)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: S1PR1 NM_001400.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S1PR1	NM_001400.5	c.-231A>G		5_prime_UTR_variant	1/2	ENST00000305352.7	NP_001391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7	c.-231A>G		5_prime_UTR_variant	1/2	1	NM_001400.5	ENSP00000305416	P1
S1PR1	ENST00000475821.2	c.-164+41A>G		intron_variant		2		ENSP00000498194
S1PR1	ENST00000561748.2	n.134A>G		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.0677 AC: 10298 AN: 152072 Hom.: 596 Cov.: 30

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.0488

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0749

GnomAD4 exome AF: 0.0294 AC: 3 AN: 102 Hom.: 0 Cov.: 0 AF XY: 0.0294 AC XY: 2 AN XY: 68

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.0156

Gnomad4 NFE exome AF: 0.0667

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0676 AC: 10293 AN: 152190 Hom.: 595 Cov.: 30 AF XY: 0.0701 AC XY: 5217 AN XY: 74400

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.0486

Gnomad4 FIN AF: 0.0767

Gnomad4 NFE AF: 0.0541

Gnomad4 OTH AF: 0.0746

Alfa AF: 0.0610 Hom.: 71

Bravo AF: 0.0673

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3765684; hg19: chr1-101702588;