Genetic Variant NM_003775.4:c.148C>G (chr19-3178940-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003775.4(S1PR4):c.148C>G(p.Arg50Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000578 in 1,383,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R50W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

S1PR4
NM_003775.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.440

Publications

1 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:

ENSG00000289471 (HGNC:):

ENSG00000289471 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18892804).

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.148C>G	p.Arg50Gly	missense	Exon 1 of 1	NP_003766.1	O95977

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
S1PR4	ENST00000246115.5	TSL:6 MANE Select	c.148C>G	p.Arg50Gly	missense	Exon 1 of 1	ENSP00000246115.3	O95977
S1PR4	ENST00000591346.1	TSL:3	n.100-274C>G		intron	N/A
ENSG00000289471	ENST00000687895.2		n.-232G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000150

AC:

AN:

133364

AF XY:

0.0000135

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000578

AC:

AN:

1383014

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

682924

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31394

American (AMR)

AF:

0.00

AC:

AN:

35420

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24396

East Asian (EAS)

AF:

0.00

AC:

AN:

35866

South Asian (SAS)

AF:

0.0000758

AC:

AN:

79206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4192

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078708

Other (OTH)

AF:

0.0000174

AC:

AN:

57528

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000185

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.085

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.5

PhyloP100

0.44

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.99

REVEL

Benign

0.10

Sift

Benign

0.20

Sift4G

Benign

0.39

Polyphen

0.45

Vest4

0.39

MutPred

0.58

Loss of helix (P = 0.0033)

MVP

0.36

MPC

0.83

ClinPred

0.11

GERP RS

1.5

PromoterAI

-0.041

Neutral

(source)

Varity_R

0.056

gMVP

0.53

Mutation Taster

=91/9

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over