19-3178940-C-A

Variant names:

• chr19-3178940-C-A
• rs779388175
• NM_003775.4:c.148C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003775.4(S1PR4):​c.148C>A​(p.Arg50Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,016 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: S1PR4 NM_003775.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.44 with no splicing effect.

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>A	p.Arg50Arg	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.148C>A	p.Arg50Arg	synonymous	Exon 1 of 1	ENSP00000246115.3	O95977
	S1PR4	ENST00000591346.1	TSL:3	n.100-274C>A		intron	N/A
	ENSG00000289471	ENST00000687895.2		n.-232G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383016 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 682924

African (AFR) AF: 0.00 AC: 0 AN: 31396

American (AMR) AF: 0.00 AC: 0 AN: 35420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24396

East Asian (EAS) AF: 0.00 AC: 0 AN: 35866

South Asian (SAS) AF: 0.00 AC: 0 AN: 79206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36304

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4192

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078708

Other (OTH) AF: 0.00 AC: 0 AN: 57528

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.2
DANN	Benign	0.87
PhyloP100		0.44
PromoterAI		-0.032	Neutral

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

Other links and lift over

dbSNP: rs779388175; hg19: chr19-3178938;