ENST00000697990.2:c.465-39487C>T

Variant names:

• chr10-70914732-C-T
• rs12415816
• ENST00000697990.2:c.465-39487C>T

Variant summary

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

The ENST00000697990.2(SGPL1):​c.465-39487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,088 control chromosomes in the GnomAD database, including 14,995 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 0.43 (14995 hom., cov: 32)
• Consequence: SGPL1 ENST00000697990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.827
• Publications: 1 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: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000697990.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGPL1	ENST00000697990.2		c.465-39487C>T		intron	N/A	ENSP00000520631.1	A0ABB0MV32

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64686 AN: 151970 Hom.: 14998 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.425 AC: 64694 AN: 152088 Hom.: 14995 Cov.: 32 AF XY: 0.426 AC XY: 31652 AN XY: 74346

African (AFR) AF: 0.235 AC: 9764 AN: 41500

American (AMR) AF: 0.524 AC: 8011 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1604 AN: 3466

East Asian (EAS) AF: 0.385 AC: 1988 AN: 5162

South Asian (SAS) AF: 0.503 AC: 2424 AN: 4818

European-Finnish (FIN) AF: 0.470 AC: 4974 AN: 10584

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.509 AC: 34583 AN: 67962

Other (OTH) AF: 0.416 AC: 877 AN: 2106

Alfa AF: 0.485 Hom.: 33657

Bravo AF: 0.422

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.76
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs12415816; hg19: chr10-72674489;