ENST00000697990.2:c.465-25605T>C

Variant names:

• chr10-70928614-T-C
• rs1466576
• ENST00000697990.2:c.465-25605T>C

Variant summary

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

The ENST00000697990.2(SGPL1):​c.465-25605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,760 control chromosomes in the GnomAD database, including 9,256 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 0.34 (9256 hom., cov: 31)
• Consequence: SGPL1 ENST00000697990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98
• Publications: 6 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]

ENSG00000285300 (HGNC:):

LINC02622 (HGNC:54099): (long intergenic non-protein coding RNA 2622)

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 = 0.405 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.465-25605T>C		intron_variant	Intron 7 of 7			ENSP00000520631.1
ENSG00000285300	ENST00000646051.1	n.164+1396T>C		intron_variant	Intron 1 of 4
LINC02622	ENST00000698069.1	n.197+9652T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51283 AN: 151642 Hom.: 9248 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.338 AC: 51307 AN: 151760 Hom.: 9256 Cov.: 31 AF XY: 0.333 AC XY: 24668 AN XY: 74152

African (AFR) AF: 0.271 AC: 11211 AN: 41352

American (AMR) AF: 0.414 AC: 6307 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 958 AN: 3464

East Asian (EAS) AF: 0.0882 AC: 454 AN: 5150

South Asian (SAS) AF: 0.249 AC: 1199 AN: 4816

European-Finnish (FIN) AF: 0.343 AC: 3608 AN: 10522

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.392 AC: 26607 AN: 67890

Other (OTH) AF: 0.314 AC: 664 AN: 2112

Alfa AF: 0.367 Hom.: 22515

Bravo AF: 0.341

Asia WGS AF: 0.194 AC: 679 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.37
PhyloP100		-3.0

Splicing

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

Other links and lift over

dbSNP: rs1466576; hg19: chr10-72688371;