chr19-3178904-C-A

Variant names:

• chr19-3178904-C-A
• rs768321040
• NM_003775.4:c.112C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003775.4(S1PR4):​c.112C>A​(p.Arg38Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,370,008 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: S1PR4 NM_003775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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]

ENSG00000289471 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR4	NM_003775.4	c.112C>A	p.Arg38Ser	missense_variant	Exon 1 of 1	ENST00000246115.5	NP_003766.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR4	ENST00000246115.5	c.112C>A	p.Arg38Ser	missense_variant	Exon 1 of 1	6	NM_003775.4	ENSP00000246115.3
S1PR4	ENST00000591346.1	n.100-310C>A		intron_variant	Intron 1 of 1	3
ENSG00000289471	ENST00000687895.2	n.-196G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1370008 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675596

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.32e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.57	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.37
Sift	Benign	0.084	T
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.37		Gain of glycosylation at R38 (P = 0.0012);
MVP		0.68
MPC		1.3
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.26
gMVP		0.83

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

LitVar

Other links and lift over

dbSNP: rs768321040; hg19: chr19-3178902;