dbSNP rs34573539: S1PR4:p.Thr95Thr (chr19-3179077-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_003775.4(S1PR4):c.285G>A(p.Thr95Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 1,610,354 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 49 hom. )

Consequence

S1PR4
NM_003775.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.50

Publications

0 publications found

Variant links:

Genes affected

S1PR4 (HGNC:3170): (sphingosine-1-phosphate receptor 4) This gene is a member of the endothelial differentiation, G-protein-coupled (EDG)) receptor gene family. EDG receptors bind lysophospholipids or lysosphingolipids as ligands, and are involved in cell signalling in many different cell types. This EDG receptor gene is intronless and is specifically expressed in the lymphoid tissue. [provided by RefSeq, Jul 2008]

S1PR4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 19-3179077-G-A is Benign according to our data. Variant chr19-3179077-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 771510.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.5 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003775.4. 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
	S1PR4	NM_003775.4	MANE Select	c.285G>A	p.Thr95Thr	synonymous	Exon 1 of 1	NP_003766.1	O95977

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S1PR4	ENST00000246115.5	TSL:6 MANE Select	c.285G>A	p.Thr95Thr	synonymous	Exon 1 of 1	ENSP00000246115.3	O95977
	S1PR4	ENST00000591346.1	TSL:3	n.100-137G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00535

AC:

814

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00497

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00767

Gnomad OTH

AF:

0.00573

GnomAD2 exomes

AF:

0.00668

AC:

1598

AN:

239048

AF XY:

0.00689

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00364

Gnomad ASJ exome

AF:

0.00380

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0126

Gnomad NFE exome

AF:

0.00924

Gnomad OTH exome

AF:

0.00792

GnomAD4 exome

AF:

0.00685

AC:

9993

AN:

1458024

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

4974

AN XY:

725382

show subpopulations

African (AFR)

AF:

0.00105

AC:

AN:

33470

American (AMR)

AF:

0.00401

AC:

179

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.00368

AC:

AN:

26102

East Asian (EAS)

AF:

0.000101

AC:

AN:

39688

South Asian (SAS)

AF:

0.00510

AC:

440

AN:

86246

European-Finnish (FIN)

AF:

0.0119

AC:

596

AN:

50044

Middle Eastern (MID)

AF:

0.00801

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00740

AC:

8230

AN:

1111740

Other (OTH)

AF:

0.00609

AC:

367

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

608

1215

1823

2430

3038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.00533

AC:

812

AN:

152330

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

404

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41588

American (AMR)

AF:

0.00294

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00477

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0139

AC:

148

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00767

AC:

522

AN:

68020

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00506

Hom.:

Bravo

AF:

0.00433

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00848

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.20

(source)

DANN

Benign

0.97

PhyloP100

-4.5

PromoterAI

-0.016

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over