1-101238940-T-C

Position:

• chr1-101238940-T-C

Variant summary

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

The NM_001400.5(S1PR1):​c.-45T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 1,559,516 control chromosomes in the GnomAD database, including 5,193 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 0.084 (674 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4519 hom.)
• Consequence: S1PR1 NM_001400.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S1PR1	NM_001400.5	c.-45T>C		5_prime_UTR_variant	2/2	ENST00000305352.7	NP_001391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7	c.-45T>C		5_prime_UTR_variant	2/2	1	NM_001400.5	ENSP00000305416	P1

Frequencies

GnomAD3 genomes AF: 0.0838 AC: 12761 AN: 152214 Hom.: 675 Cov.: 32

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0615

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.0770

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.0920

GnomAD3 exomes AF: 0.0935 AC: 18042 AN: 193050 Hom.: 1194 AF XY: 0.0931 AC XY: 9714 AN XY: 104298

Gnomad AFR exome AF: 0.0874

Gnomad AMR exome AF: 0.0633

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.284

Gnomad SAS exome AF: 0.0855

Gnomad FIN exome AF: 0.0957

Gnomad NFE exome AF: 0.0690

Gnomad OTH exome AF: 0.0819

GnomAD4 exome AF: 0.0728 AC: 102437 AN: 1407184 Hom.: 4519 Cov.: 28 AF XY: 0.0734 AC XY: 51053 AN XY: 695852

Gnomad4 AFR exome AF: 0.0865

Gnomad4 AMR exome AF: 0.0614

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.231

Gnomad4 SAS exome AF: 0.0876

Gnomad4 FIN exome AF: 0.0919

Gnomad4 NFE exome AF: 0.0630

Gnomad4 OTH exome AF: 0.0867

GnomAD4 genome AF: 0.0837 AC: 12755 AN: 152332 Hom.: 674 Cov.: 32 AF XY: 0.0864 AC XY: 6439 AN XY: 74486

Gnomad4 AFR AF: 0.0885

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.0764

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.0694

Gnomad4 OTH AF: 0.0905

Alfa AF: 0.0742 Hom.: 525

Bravo AF: 0.0823

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.3
DANN	Benign	0.65

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: rs3737578; hg19: chr1-101704496; COSMIC: COSV59514831; COSMIC: COSV59514831;