rs1880057

Positions:

• chr10-70866790-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003901.4(SGPL1):​c.616-1555T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,308 control chromosomes in the GnomAD database, including 1,346 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 0.12 (1346 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: SGPL1 NM_003901.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

Genes affected

SGPL1 (HGNC:10817): (sphingosine-1-phosphate lyase 1) Enables sphinganine-1-phosphate aldolase activity. Involved in apoptotic signaling pathway; fatty acid metabolic process; and sphingolipid metabolic process. Located in endoplasmic reticulum. Implicated in nephrotic syndrome type 14. [provided by Alliance of Genome Resources, Apr 2022]

SGPL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGPL1	NM_003901.4	c.616-1555T>C		intron_variant		ENST00000373202.8	NP_003892.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGPL1	ENST00000373202.8	c.616-1555T>C		intron_variant		1	NM_003901.4	ENSP00000362298.3

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18147 AN: 152186 Hom.: 1346 Cov.: 32

Gnomad AFR AF: 0.0423

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.250

GnomAD4 genome AF: 0.119 AC: 18138 AN: 152304 Hom.: 1346 Cov.: 32 AF XY: 0.115 AC XY: 8550 AN XY: 74468

Gnomad4 AFR AF: 0.0421

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.0866

Gnomad4 SAS AF: 0.0689

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.124

Alfa AF: 0.153 Hom.: 981

Bravo AF: 0.114

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.71

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: rs1880057; hg19: chr10-72626547;