1-101237269-A-G

Variant names:

• chr1-101237269-A-G
• rs3753194
• NM_001400.5:c.-164+170A>G

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+170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0702 in 152,182 control chromosomes in the GnomAD database, including 609 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 0.070 (609 hom., cov: 31)
• Consequence: S1PR1 NM_001400.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR1	NM_001400.5	c.-164+170A>G		intron_variant	Intron 1 of 1	ENST00000305352.7	NP_001391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7	c.-164+170A>G		intron_variant	Intron 1 of 1	1	NM_001400.5	ENSP00000305416.6
S1PR1	ENST00000475821.2	c.-164+278A>G		intron_variant	Intron 1 of 1	2		ENSP00000498194.1
S1PR1	ENST00000561748.2	n.201+170A>G		intron_variant	Intron 1 of 2	6
S1PR1	ENST00000649383.1	c.-660A>G		upstream_gene_variant				ENSP00000497175.1

Frequencies

GnomAD3 genomes AF: 0.0703 AC: 10689 AN: 152064 Hom.: 610 Cov.: 31

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0500

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0584

Gnomad OTH AF: 0.0764

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

GnomAD4 genome AF: 0.0702 AC: 10684 AN: 152182 Hom.: 609 Cov.: 31 AF XY: 0.0727 AC XY: 5407 AN XY: 74412

African (AFR) AF: 0.0619 AC: 2569 AN: 41530

American (AMR) AF: 0.0500 AC: 765 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 469 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1618 AN: 5168

South Asian (SAS) AF: 0.0491 AC: 237 AN: 4826

European-Finnish (FIN) AF: 0.0778 AC: 824 AN: 10590

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

European-Non Finnish (NFE) AF: 0.0584 AC: 3968 AN: 67972

Other (OTH) AF: 0.0761 AC: 161 AN: 2116

Alfa AF: 0.0606 Hom.: 631

Bravo AF: 0.0696

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.35
PhyloP100		0.21
PromoterAI		-0.024	Neutral
Mutation Taster		=100/0	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: rs3753194; hg19: chr1-101702825; COSMIC: COSV59514687; COSMIC: COSV59514687;