Genetic Variant NM_001320730.2:c.-165G>C (chr1-101236990-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001320730.2(S1PR1):c.-165G>C variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 148,956 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.069 ( 589 hom., cov: 30)

Exomes 𝑓: 0.048 ( 0 hom. )

Consequence

S1PR1
NM_001320730.2 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.02

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320730.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
S1PR1	NM_001320730.2	c.-165G>C	splice_region	Exon 1 of 2	NP_001307659.1
S1PR1	NM_001320730.2	c.-165G>C	5_prime_UTR	Exon 1 of 2	NP_001307659.1
S1PR1	NR_174348.1	n.92G>C	splice_region non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
S1PR1	ENST00000945457.1		c.-252G>C	splice_region	Exon 1 of 3	ENSP00000615516.1
S1PR1	ENST00000475821.2	TSL:2	c.-165G>C	splice_region	Exon 1 of 2	ENSP00000498194.1
S1PR1	ENST00000876129.1		c.-360G>C	5_prime_UTR	Exon 1 of 3	ENSP00000546188.1

Frequencies

GnomAD3 genomes

AF:

0.0695

AC:

10339

AN:

148694

Hom.:

590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0680

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.0496

Gnomad FIN

AF:

0.0771

Gnomad MID

AF:

0.0548

Gnomad NFE

AF:

0.0542

Gnomad OTH

AF:

0.0761

GnomAD4 exome

AF:

0.0479

AC:

AN:

146

Hom.:

Cov.:

AF XY:

0.0600

AC XY:

AN XY:

100

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.0405

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0577

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.0695

AC:

10337

AN:

148810

Hom.:

589

Cov.:

AF XY:

0.0720

AC XY:

5232

AN XY:

72706

show subpopulations

African (AFR)

AF:

0.0678

AC:

2628

AN:

38766

American (AMR)

AF:

0.0496

AC:

752

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

456

AN:

3458

East Asian (EAS)

AF:

0.311

AC:

1587

AN:

5102

South Asian (SAS)

AF:

0.0494

AC:

232

AN:

4696

European-Finnish (FIN)

AF:

0.0771

AC:

814

AN:

10560

Middle Eastern (MID)

AF:

0.0590

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0542

AC:

3673

AN:

67810

Other (OTH)

AF:

0.0758

AC:

157

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

480

960

1440

1920

2400

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:

0.0614

Hom.:

Bravo

AF:

0.0675

Asia WGS

AF:

0.153

AC:

526

AN:

3444

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.4

(source)

DANN

Benign

0.88

PhyloP100

-2.0

PromoterAI

-0.061

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over