rs1358733

chr1-101243291-T-Achr1-101243291-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000561748.2(S1PR1):n.1549T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,148 control chromosomes in the GnomAD database, including 4,212 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 0.21 (4212 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: S1PR1 ENST00000561748.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S1PR1	ENST00000561748.2	n.1549T>A		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32136 AN: 152030 Hom.: 4216 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.205

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.211 AC: 32136 AN: 152148 Hom.: 4212 Cov.: 32 AF XY: 0.216 AC XY: 16081 AN XY: 74378

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.702

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.202

Alfa AF: 0.187 Hom.: 318

Bravo AF: 0.215

Asia WGS AF: 0.392 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.1
Dann	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1358733; hg19: chr1-101708847;