1-101237269-A-G

Position:

• chr1-101237269-A-G

Variant summary

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

The ENST00000305352.7(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 ENST00000305352.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213

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=-0.83).
• 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/exons	MANE	Protein	UniProt
S1PR1	NM_001400.5	c.-164+170A>G		intron_variant		ENST00000305352.7	NP_001391.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7	c.-164+170A>G		intron_variant		1	NM_001400.5	ENSP00000305416	P1
S1PR1	ENST00000475821.2	c.-164+278A>G		intron_variant		2		ENSP00000498194
S1PR1	ENST00000561748.2	n.201+170A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.0500

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0778

Gnomad4 NFE AF: 0.0584

Gnomad4 OTH AF: 0.0761

Alfa AF: 0.0610 Hom.: 453

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

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: rs3753194; hg19: chr1-101702825; COSMIC: COSV59514687; COSMIC: COSV59514687;