Genetic Variant NM_001400.5:c.-9G>T (chr1-101238976-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001400.5(S1PR1):c.-9G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,607,628 control chromosomes in the GnomAD database, including 85,250 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 0.23 ( 5182 hom., cov: 33)

Exomes 𝑓: 0.32 ( 80068 hom. )

Consequence

S1PR1
NM_001400.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

Publications

16 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR1	NM_001400.5 link	c.-9G>T		5_prime_UTR_variant	Exon 2 of 2	ENST00000305352.7	NP_001391.2	P21453

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR1	ENST00000305352.7 link	c.-9G>T		5_prime_UTR_variant	Exon 2 of 2	1	NM_001400.5	ENSP00000305416.6		P21453

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34942

AN:

152162

Hom.:

5184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0618

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.150

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.244

GnomAD2 exomes

AF:

0.244

AC:

59263

AN:

242634

AF XY:

0.250

show subpopulations

Gnomad AFR exome

AF:

0.0557

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.255

Gnomad EAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.283

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.320

AC:

465976

AN:

1455348

Hom.:

80068

Cov.:

AF XY:

0.316

AC XY:

228590

AN XY:

723598

show subpopulations

African (AFR)

AF:

0.0555

AC:

1851

AN:

33356

American (AMR)

AF:

0.137

AC:

6046

AN:

44122

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

6615

AN:

25648

East Asian (EAS)

AF:

0.142

AC:

5637

AN:

39650

South Asian (SAS)

AF:

0.143

AC:

12204

AN:

85516

European-Finnish (FIN)

AF:

0.293

AC:

15524

AN:

52986

Middle Eastern (MID)

AF:

0.266

AC:

1510

AN:

5684

European-Non Finnish (NFE)

AF:

0.360

AC:

398919

AN:

1108288

Other (OTH)

AF:

0.294

AC:

17670

AN:

60098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16231

32462

48694

64925

81156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12432

24864

37296

49728

62160

<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:

0.229

AC:

34940

AN:

152280

Hom.:

5182

Cov.:

AF XY:

0.223

AC XY:

16599

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0618

AC:

2567

AN:

41564

American (AMR)

AF:

0.190

AC:

2907

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.255

AC:

884

AN:

3472

East Asian (EAS)

AF:

0.150

AC:

778

AN:

5184

South Asian (SAS)

AF:

0.132

AC:

638

AN:

4832

European-Finnish (FIN)

AF:

0.282

AC:

2996

AN:

10610

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23340

AN:

68000

Other (OTH)

AF:

0.243

AC:

512

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1337

2675

4012

5350

6687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.299

Hom.:

10288

Bravo

AF:

0.216

Asia WGS

AF:

0.114

AC:

399

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

3.4

(source)

DANN

Benign

0.73

PhyloP100

-0.066

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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