Variant chr19-10514589-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_030760.5(S1PR5):c.423G>A(p.Gly141=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00691 in 1,576,570 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 46 hom. )

Consequence

S1PR5
NM_030760.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.73

Variant links:

Genes affected

S1PR5 (HGNC:14299): (sphingosine-1-phosphate receptor 5) The lysosphingolipid sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Its actions may be both intracellular as a second messenger and extracellular as a receptor ligand. S1P and the structurally related lysolipid mediator lysophosphatidic acid (LPA) signal cells through a set of G protein-coupled receptors known as EDG receptors. Some EDG receptors (e.g., EDG1; MIM 601974) are S1P receptors; others (e.g., EDG2; MIM 602282) are LPA receptors.[supplied by OMIM, Mar 2008]

S1PR5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 19-10514589-C-T is Benign according to our data. Variant chr19-10514589-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S1PR5	NM_030760.5 linkuse as main transcript	c.423G>A	p.Gly141=	synonymous_variant	2/2	ENST00000333430.6
S1PR5	NM_001166215.2 linkuse as main transcript	c.423G>A	p.Gly141=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S1PR5	ENST00000333430.6 linkuse as main transcript	c.423G>A	p.Gly141=	synonymous_variant	2/2	1	NM_030760.5	P1	Q9H228-1
S1PR5	ENST00000439028.3 linkuse as main transcript	c.423G>A	p.Gly141=	synonymous_variant	2/2	2		P1	Q9H228-1

Frequencies

GnomAD3 genomes

AF:

0.00486

AC:

740

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00904

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00709

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00492

AC:

880

AN:

178730

Hom.:

AF XY:

0.00492

AC XY:

485

AN XY:

98560

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.0000745

Gnomad SAS exome

AF:

0.000155

Gnomad FIN exome

AF:

0.00901

Gnomad NFE exome

AF:

0.00673

Gnomad OTH exome

AF:

0.00667

GnomAD4 exome

AF:

0.00713

AC:

10158

AN:

1424268

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

4876

AN XY:

705680

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00210

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.0000265

Gnomad4 SAS exome

AF:

0.000303

Gnomad4 FIN exome

AF:

0.0102

Gnomad4 NFE exome

AF:

0.00796

Gnomad4 OTH exome

AF:

0.00661

GnomAD4 genome

AF:

0.00486

AC:

740

AN:

152302

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

319

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00152

Gnomad4 AMR

AF:

0.00235

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00904

Gnomad4 NFE

AF:

0.00709

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00732

Hom.:

Bravo

AF:

0.00457

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 07, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2022	S1PR5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.44

DANN

Benign

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over