10-89391165-G-T

Variant summary

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

The ENST00000371837.5(LIPA):c.61+21626C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,130 control chromosomes in the GnomAD database, including 31,977 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 0.62 (31977 hom., cov: 33)
• Consequence: LIPA ENST00000371837.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.874 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	ENST00000371837.5	c.61+21626C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94633 AN: 152012 Hom.: 31936 Cov.: 33

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.623 AC: 94721 AN: 152130 Hom.: 31977 Cov.: 33 AF XY: 0.624 AC XY: 46431 AN XY: 74382

Gnomad4 AFR AF: 0.882

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.618

Alfa AF: 0.511 Hom.: 27361

Bravo AF: 0.639

Asia WGS AF: 0.686 AC: 2383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.7
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs304478; hg19: chr10-91150922;