chr1-101238092-A-T

Variant names:

• chr1-101238092-A-T
• rs61780687
• NM_001400.5:c.-163-730A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001400.5(S1PR1):​c.-163-730A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,778 control chromosomes in the GnomAD database, including 6,166 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 0.26 (6159 hom., cov: 29)
  • Exomes 𝑓: 0.37 (7 hom.)
• Consequence: S1PR1 NM_001400.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 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.-163-730A>T		intron	N/A	NP_001391.2
	S1PR1	NM_001320730.2		c.-163-730A>T		intron	N/A	NP_001307659.1	P21453
	S1PR1	NR_174345.1		n.81+993A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR1	ENST00000305352.7	TSL:1 MANE Select	c.-163-730A>T		intron	N/A	ENSP00000305416.6	P21453
	S1PR1	ENST00000475289.2	TSL:3	c.-323A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000498038.1	P21453
	S1PR1	ENST00000475289.2	TSL:3	c.-323A>T		5_prime_UTR	Exon 1 of 2	ENSP00000498038.1	P21453

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38718 AN: 151586 Hom.: 6157 Cov.: 29

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.0568

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.369 AC: 31 AN: 84 Hom.: 7 Cov.: 0 AF XY: 0.351 AC XY: 26 AN XY: 74

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.414 AC: 29 AN: 70

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.255 AC: 38727 AN: 151694 Hom.: 6159 Cov.: 29 AF XY: 0.250 AC XY: 18563 AN XY: 74112

African (AFR) AF: 0.0942 AC: 3895 AN: 41352

American (AMR) AF: 0.228 AC: 3483 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 845 AN: 3468

East Asian (EAS) AF: 0.0570 AC: 292 AN: 5126

South Asian (SAS) AF: 0.266 AC: 1277 AN: 4796

European-Finnish (FIN) AF: 0.311 AC: 3262 AN: 10504

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24834 AN: 67904

Other (OTH) AF: 0.252 AC: 527 AN: 2094

Alfa AF: 0.300 Hom.: 920

Bravo AF: 0.239

Asia WGS AF: 0.152 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		-0.71
PromoterAI		-0.037	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: rs61780687; hg19: chr1-101703648;