rs3737578

Variant names:

• chr1-101238940-T-C
• rs3737578
• NM_001400.5:c.-45T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR1	NM_001400.5	MANE Select	c.-45T>C		5_prime_UTR	Exon 2 of 2	NP_001391.2
	S1PR1	NM_001320730.2		c.-45T>C		5_prime_UTR	Exon 2 of 2	NP_001307659.1	P21453
	S1PR1	NR_174347.1		n.200T>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR1	ENST00000305352.7	TSL:1 MANE Select	c.-45T>C		5_prime_UTR	Exon 2 of 2	ENSP00000305416.6	P21453
	S1PR1	ENST00000475289.2	TSL:3	c.-45T>C		5_prime_UTR	Exon 2 of 2	ENSP00000498038.1	P21453
	S1PR1	ENST00000648480.1		c.-45T>C		5_prime_UTR	Exon 2 of 2	ENSP00000497478.1	P21453

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

GnomAD2 exomes AF: 0.0935 AC: 18042 AN: 193050 AF XY: 0.0931

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 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

African (AFR) AF: 0.0865 AC: 2776 AN: 32076

American (AMR) AF: 0.0614 AC: 2309 AN: 37602

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 2918 AN: 22920

East Asian (EAS) AF: 0.231 AC: 9017 AN: 39014

South Asian (SAS) AF: 0.0876 AC: 6826 AN: 77878

European-Finnish (FIN) AF: 0.0919 AC: 4582 AN: 49842

Middle Eastern (MID) AF: 0.116 AC: 576 AN: 4960

European-Non Finnish (NFE) AF: 0.0630 AC: 68396 AN: 1084820

Other (OTH) AF: 0.0867 AC: 5037 AN: 58072

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

African (AFR) AF: 0.0885 AC: 3679 AN: 41582

American (AMR) AF: 0.0615 AC: 941 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3466

East Asian (EAS) AF: 0.264 AC: 1368 AN: 5182

South Asian (SAS) AF: 0.0764 AC: 369 AN: 4830

European-Finnish (FIN) AF: 0.0937 AC: 995 AN: 10618

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0694 AC: 4724 AN: 68028

Other (OTH) AF: 0.0905 AC: 191 AN: 2110

Alfa AF: 0.0752 Hom.: 889

Bravo AF: 0.0823

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.3
DANN	Benign	0.65
PhyloP100		-1.1
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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