chr19-10514391-A-C

Variant names:

• chr19-10514391-A-C
• rs6511701
• NM_030760.5:c.621T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_030760.5(S1PR5):​c.621T>G​(p.Ala207Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 1,602,702 control chromosomes in the GnomAD database, including 502,913 homozygotes. 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: 𝑓 0.79 (47724 hom., cov: 35)
  • Exomes 𝑓: 0.79 (455189 hom.)
• Consequence: S1PR5 NM_030760.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=1.93 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S1PR5	NM_030760.5	c.621T>G	p.Ala207Ala	synonymous_variant	Exon 2 of 2	ENST00000333430.6	NP_110387.1
S1PR5	NM_001166215.2	c.621T>G	p.Ala207Ala	synonymous_variant	Exon 2 of 2		NP_001159687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S1PR5	ENST00000333430.6	c.621T>G	p.Ala207Ala	synonymous_variant	Exon 2 of 2	1	NM_030760.5	ENSP00000328472.3
S1PR5	ENST00000439028.3	c.621T>G	p.Ala207Ala	synonymous_variant	Exon 2 of 2	2		ENSP00000416915.2

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120221 AN: 152084 Hom.: 47680 Cov.: 35

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.783

GnomAD2 exomes AF: 0.805 AC: 183390 AN: 227918 AF XY: 0.807

Gnomad AFR exome AF: 0.770

Gnomad AMR exome AF: 0.863

Gnomad ASJ exome AF: 0.750

Gnomad EAS exome AF: 0.767

Gnomad FIN exome AF: 0.808

Gnomad NFE exome AF: 0.779

Gnomad OTH exome AF: 0.790

GnomAD4 exome AF: 0.791 AC: 1147930 AN: 1450506 Hom.: 455189 Cov.: 82 AF XY: 0.793 AC XY: 571779 AN XY: 720590

African (AFR) AF: 0.776 AC: 25844 AN: 33310

American (AMR) AF: 0.860 AC: 36861 AN: 42846

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 19559 AN: 25894

East Asian (EAS) AF: 0.829 AC: 32486 AN: 39192

South Asian (SAS) AF: 0.886 AC: 74995 AN: 84632

European-Finnish (FIN) AF: 0.807 AC: 41591 AN: 51540

Middle Eastern (MID) AF: 0.768 AC: 4417 AN: 5748

European-Non Finnish (NFE) AF: 0.781 AC: 865000 AN: 1107426

Other (OTH) AF: 0.787 AC: 47177 AN: 59918

GnomAD4 genome AF: 0.791 AC: 120319 AN: 152196 Hom.: 47724 Cov.: 35 AF XY: 0.793 AC XY: 59019 AN XY: 74390

African (AFR) AF: 0.776 AC: 32259 AN: 41546

American (AMR) AF: 0.830 AC: 12695 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2594 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4009 AN: 5144

South Asian (SAS) AF: 0.894 AC: 4322 AN: 4832

European-Finnish (FIN) AF: 0.800 AC: 8483 AN: 10610

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.786 AC: 53442 AN: 67980

Other (OTH) AF: 0.784 AC: 1659 AN: 2116

Alfa AF: 0.779 Hom.: 24169

Bravo AF: 0.789

Asia WGS AF: 0.864 AC: 3002 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.4
DANN	Benign	0.26
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs6511701; hg19: chr19-10625067; COSMIC: COSV61013344; COSMIC: COSV61013344;