rs7922193

chr10-89261888-G-Achr10-89261888-G-C

Variant summary

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

The ENST00000371837.5(LIPA):c.62-33490C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,958 control chromosomes in the GnomAD database, including 15,925 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 0.45 (15925 hom., cov: 32)
• Consequence: LIPA ENST00000371837.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

Genes affected

LIPA (HGNC:6617): (lipase A, lysosomal acid type) This gene encodes lipase A, the lysosomal acid lipase (also known as cholesterol ester hydrolase). This enzyme functions in the lysosome to catalyze the hydrolysis of cholesteryl esters and triglycerides. Mutations in this gene can result in Wolman disease and cholesteryl ester storage disease. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPA	ENST00000282673.5	c.-1-14239C>T		intron_variant		3
LIPA	ENST00000371837.5	c.62-33490C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68140 AN: 151840 Hom.: 15914 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.449 AC: 68189 AN: 151958 Hom.: 15925 Cov.: 32 AF XY: 0.455 AC XY: 33763 AN XY: 74248

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.460

Alfa AF: 0.439 Hom.: 7012

Bravo AF: 0.457

Asia WGS AF: 0.627 AC: 2178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.88
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7922193; hg19: chr10-91021645;