rs12409786

Variant names:

• chr1-101243196-T-C
• rs12409786
• ENST00000561748.2:n.1454T>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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000561748.2	n.1454T>C		non_coding_transcript_exon_variant	Exon 3 of 3	6

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;