rs4746070

Variant names:

• chr10-70913850-T-C
• rs4746070
• ENST00000697990.2:c.465-40369T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000697990.2(SGPL1):​c.465-40369T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,146 control chromosomes in the GnomAD database, including 35,331 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 0.67 (35331 hom., cov: 33)
• Consequence: SGPL1 ENST00000697990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.550
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome 14

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGPL1	ENST00000697990.2	c.465-40369T>C		intron_variant	Intron 7 of 7			ENSP00000520631.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102387 AN: 152028 Hom.: 35311 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.679

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.673 AC: 102457 AN: 152146 Hom.: 35331 Cov.: 33 AF XY: 0.678 AC XY: 50445 AN XY: 74374

African (AFR) AF: 0.530 AC: 21978 AN: 41458

American (AMR) AF: 0.755 AC: 11541 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2147 AN: 3472

East Asian (EAS) AF: 0.632 AC: 3267 AN: 5168

South Asian (SAS) AF: 0.727 AC: 3507 AN: 4826

European-Finnish (FIN) AF: 0.819 AC: 8698 AN: 10614

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.723 AC: 49145 AN: 67998

Other (OTH) AF: 0.678 AC: 1434 AN: 2116

Alfa AF: 0.710 Hom.: 61178

Bravo AF: 0.663

Asia WGS AF: 0.681 AC: 2369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.83
PhyloP100		0.55

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4746070; hg19: chr10-72673607;