Genetic Variant NM_001400.5:c.-231A>G (chr1-101237032-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001400.5(S1PR1):c.-231A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 152,292 control chromosomes in the GnomAD database, including 595 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 0.068 ( 595 hom., cov: 30)

Exomes 𝑓: 0.029 ( 0 hom. )

Consequence

S1PR1
NM_001400.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.149

Publications

5 publications found

Variant links:

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]

S1PR1 links:

S1PR1-DT (HGNC:55842): (S1PR1 divergent transcript)

S1PR1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR1	NM_001400.5 link	c.-231A>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000305352.7	NP_001391.2	P21453

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
S1PR1	ENST00000305352.7 link	c.-231A>G	5_prime_UTR_variant	Exon 1 of 2	1	NM_001400.5	ENSP00000305416.6	P21453
S1PR1	ENST00000561748.2 link	n.134A>G	non_coding_transcript_exon_variant	Exon 1 of 3	6
S1PR1	ENST00000475821.2 link	c.-164+41A>G	intron_variant	Intron 1 of 1	2		ENSP00000498194.1	A0A3B3IUD4
S1PR1-DT	ENST00000686331.3 link	n.-217T>C	upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0677

AC:

10298

AN:

152072

Hom.:

596

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0611

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.0488

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.0488

Gnomad FIN

AF:

0.0767

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0749

GnomAD4 exome

AF:

0.0294

AC:

AN:

102

Hom.:

Cov.:

AF XY:

0.0294

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.0156

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0667

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0676

AC:

10293

AN:

152190

Hom.:

595

Cov.:

AF XY:

0.0701

AC XY:

5217

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0609

AC:

2532

AN:

41570

American (AMR)

AF:

0.0487

AC:

745

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

465

AN:

3470

East Asian (EAS)

AF:

0.317

AC:

1633

AN:

5152

South Asian (SAS)

AF:

0.0486

AC:

234

AN:

4816

European-Finnish (FIN)

AF:

0.0767

AC:

813

AN:

10598

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0541

AC:

3676

AN:

67978

Other (OTH)

AF:

0.0746

AC:

157

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

469

937

1406

1874

2343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0659

Hom.:

256

Bravo

AF:

0.0673

Asia WGS

AF:

0.152

AC:

529

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.15

PromoterAI

-0.062

Neutral

(source)

Mutation Taster

=294/6

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over