rs3737577

chr1-101238976-G-T

Variant summary

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

The NM_001400.5(S1PR1):c.-9G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,607,628 control chromosomes in the GnomAD database, including 85,250 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 0.23 (5182 hom., cov: 33)
  • Exomes 𝑓: 0.32 (80068 hom.)
• Consequence: S1PR1 NM_001400.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S1PR1	NM_001400.5	c.-9G>T		5_prime_UTR_variant	2/2	ENST00000305352.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S1PR1	ENST00000305352.7	c.-9G>T		5_prime_UTR_variant	2/2	1	NM_001400.5	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34942 AN: 152162 Hom.: 5184 Cov.: 33

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.244

GnomAD3 exomes AF: 0.244 AC: 59263 AN: 242634 Hom.: 8544 AF XY: 0.250 AC XY: 32935 AN XY: 131636

Gnomad AFR exome AF: 0.0557

Gnomad AMR exome AF: 0.127

Gnomad ASJ exome AF: 0.255

Gnomad EAS exome AF: 0.145

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.283

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.320 AC: 465976 AN: 1455348 Hom.: 80068 Cov.: 36 AF XY: 0.316 AC XY: 228590 AN XY: 723598

Gnomad4 AFR exome AF: 0.0555

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 0.294

GnomAD4 genome AF: 0.229 AC: 34940 AN: 152280 Hom.: 5182 Cov.: 33 AF XY: 0.223 AC XY: 16599 AN XY: 74462

Gnomad4 AFR AF: 0.0618

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.243

Alfa AF: 0.309 Hom.: 8609

Bravo AF: 0.216

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	3.4
Dann	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3737577; hg19: chr1-101704532;