rs12409786

Positions:

• chr1-101243196-T-C

Variant summary

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

The ENST00000561748.2(S1PR1):​n.1454T>C 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 0.0898 in 152,296 control chromosomes in the GnomAD database, including 767 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 0.090 (767 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: S1PR1 ENST00000561748.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.371

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000561748.2	n.1454T>C		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes AF: 0.0899 AC: 13685 AN: 152178 Hom.: 768 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0700

Gnomad OTH AF: 0.0941

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: 0.0898 AC: 13681 AN: 152296 Hom.: 767 Cov.: 32 AF XY: 0.0920 AC XY: 6849 AN XY: 74460

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0653

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.0700

Gnomad4 OTH AF: 0.0926

Alfa AF: 0.0756 Hom.: 615

Bravo AF: 0.0914

Asia WGS AF: 0.171 AC: 596 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12409786; hg19: chr1-101708752; COSMIC: COSV59514690;