rs4987248

chr1-101236990-G-Cchr1-101236990-G-T

Variant summary

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

The NM_001320730.2(S1PR1):c.-165G>C variant causes a splice region, 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 148,956 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.069 (589 hom., cov: 30)
  • Exomes 𝑓: 0.048 (0 hom.)
• Consequence: S1PR1 NM_001320730.2 splice_region, 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 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.-165G>C		splice_region_variant, 5_prime_UTR_variant	1/2	2
S1PR1	ENST00000561748.2	n.92G>C		non_coding_transcript_exon_variant	1/3
S1PR1	ENST00000305352.7			upstream_gene_variant		1	NM_001400.5	P1

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10339 AN: 148694 Hom.: 590 Cov.: 30

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.0231

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.0771

Gnomad MID AF: 0.0548

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0761

GnomAD4 exome AF: 0.0479 AC: 7 AN: 146 Hom.: 0 Cov.: 0 AF XY: 0.0600 AC XY: 6 AN XY: 100

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0405

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0577

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0695 AC: 10337 AN: 148810 Hom.: 589 Cov.: 30 AF XY: 0.0720 AC XY: 5232 AN XY: 72706

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.0496

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.0494

Gnomad4 FIN AF: 0.0771

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0758

Alfa AF: 0.0614 Hom.: 36

Bravo AF: 0.0675

Asia WGS AF: 0.153 AC: 526 AN: 3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	6.4
Dann	Benign	0.88

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: rs4987248; hg19: chr1-101702546;