10-89243088-C-T

Variant summary

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

The NM_000235.4(LIPA):c.229+2588G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,976 control chromosomes in the GnomAD database, including 24,935 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 0.57 (24935 hom., cov: 32)
• Consequence: LIPA NM_000235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPA	NM_000235.4	c.229+2588G>A		intron_variant		ENST00000336233.10
LIPA	NM_001127605.3	c.229+2588G>A		intron_variant
LIPA	NM_001288979.2	c.-120+8649G>A		intron_variant
LIPA	XM_024448023.2	c.229+2588G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPA	ENST00000336233.10	c.229+2588G>A		intron_variant		1	NM_000235.4	P1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86066 AN: 151858 Hom.: 24898 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.567 AC: 86164 AN: 151976 Hom.: 24935 Cov.: 32 AF XY: 0.569 AC XY: 42252 AN XY: 74288

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.565

Alfa AF: 0.542 Hom.: 4902

Bravo AF: 0.571

Asia WGS AF: 0.634 AC: 2207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.3
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1320496; hg19: chr10-91002845;