1-101237693-T-C

Variant names:

• chr1-101237693-T-C
• rs1411017
• NM_001400.5:c.-164+594T>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.-164+594T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,104 control chromosomes in the GnomAD database, including 2,538 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 0.12 (2538 hom., cov: 31)
• Consequence: S1PR1 NM_001400.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 2 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 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.-164+594T>C		intron	N/A	NP_001391.2
	S1PR1	NM_001320730.2		c.-164+702T>C		intron	N/A	NP_001307659.1	P21453
	S1PR1	NR_174345.1		n.81+594T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR1	ENST00000305352.7	TSL:1 MANE Select	c.-164+594T>C		intron	N/A	ENSP00000305416.6	P21453
	S1PR1	ENST00000649383.1		c.-236T>C		5_prime_UTR	Exon 1 of 2	ENSP00000497175.1	P21453
	S1PR1	ENST00000876129.1		c.-236T>C		5_prime_UTR	Exon 2 of 3	ENSP00000546188.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18570 AN: 151986 Hom.: 2536 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0531

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.0845

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0331

Gnomad OTH AF: 0.110

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.122 AC: 18588 AN: 152104 Hom.: 2538 Cov.: 31 AF XY: 0.119 AC XY: 8835 AN XY: 74384

African (AFR) AF: 0.335 AC: 13868 AN: 41434

American (AMR) AF: 0.0673 AC: 1029 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0531 AC: 184 AN: 3466

East Asian (EAS) AF: 0.0856 AC: 443 AN: 5178

South Asian (SAS) AF: 0.0840 AC: 405 AN: 4824

European-Finnish (FIN) AF: 0.0141 AC: 150 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0331 AC: 2254 AN: 67998

Other (OTH) AF: 0.109 AC: 230 AN: 2106

Alfa AF: 0.0543 Hom.: 884

Bravo AF: 0.136

Asia WGS AF: 0.100 AC: 350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		1.1
PromoterAI		0.035	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1411017; hg19: chr1-101703249;