rs3835397

chr1-101236991-AG-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The NM_001320730.2(S1PR1):c.-164+1del variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 152,120 control chromosomes in the GnomAD database, including 1,148 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.090 (1148 hom., cov: 29)
  • Exomes 𝑓: 0.041 (0 hom.)
• Consequence: S1PR1 NM_001320730.2 splice_donor
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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 Likely_benign. Variant got -6 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.080069624 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S1PR1	NM_001400.5			upstream_gene_variant		ENST00000305352.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S1PR1	ENST00000475821.2	c.-164+1del		splice_donor_variant		2
S1PR1	ENST00000561748.2	n.94del		non_coding_transcript_exon_variant	1/3
S1PR1	ENST00000305352.7			upstream_gene_variant		1	NM_001400.5	P1

Frequencies

GnomAD3 genomes AF: 0.0897 AC: 13614 AN: 151852 Hom.: 1147 Cov.: 29

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0574

Gnomad SAS AF: 0.0857

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0882

GnomAD4 exome AF: 0.0405 AC: 6 AN: 148 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 5 AN XY: 100

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0513

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0200

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0896 AC: 13621 AN: 151972 Hom.: 1148 Cov.: 29 AF XY: 0.0879 AC XY: 6530 AN XY: 74304

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.0573

Gnomad4 SAS AF: 0.0858

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0364

Gnomad4 OTH AF: 0.0868

Alfa AF: 0.0115 Hom.: 2

Bravo AF: 0.0971

Asia WGS AF: 0.0870 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs3835397; hg19: chr1-101702547;