rs1466576

Positions:

• chr10-70928614-T-C

Variant summary

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

The ENST00000697990.1(ENSG00000289738):​n.816-25605T>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: ENSG00000289738 ENST00000697990.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.98

Genes affected

ENSG00000285300 (HGNC:):

ENSG00000289738 (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]

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000285300	ENST00000646051.1	n.164+1396T>C		intron_variant
ENSG00000289738	ENST00000697990.1	n.816-25605T>C		intron_variant				ENSP00000520631.1
LINC02622	ENST00000698069.1	n.197+9652T>C		intron_variant

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

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.0882

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.314

Alfa AF: 0.374 Hom.: 14798

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1466576; hg19: chr10-72688371;