10-89279224-C-T

Variant names:

• chr10-89279224-C-T
• rs10430719
• ENST00000487618.5:n.279-721G>A

Variant summary

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

The NM_001440836.1(LIPA):​c.132-31575G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,104 control chromosomes in the GnomAD database, including 3,903 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 0.19 (3903 hom., cov: 32)
• Consequence: LIPA NM_001440836.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 2 publications found

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]

LIPA Gene-Disease associations (from GenCC):

• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• cholesteryl ester storage disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Wolman disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440836.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	NM_001440836.1		c.132-31575G>A		intron	N/A	NP_001427765.1
	LIPA	NM_001440838.1		c.15-31575G>A		intron	N/A	NP_001427767.1
	LIPA	NM_001440819.1		c.-1-31575G>A		intron	N/A	NP_001427748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	ENST00000487618.5	TSL:1	n.279-721G>A		intron	N/A
	LIPA	ENST00000868661.1		c.-1-31575G>A		intron	N/A	ENSP00000538720.1
	LIPA	ENST00000868662.1		c.-1-31575G>A		intron	N/A	ENSP00000538721.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29390 AN: 151986 Hom.: 3903 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.193 AC: 29416 AN: 152104 Hom.: 3903 Cov.: 32 AF XY: 0.206 AC XY: 15329 AN XY: 74318

African (AFR) AF: 0.117 AC: 4844 AN: 41502

American (AMR) AF: 0.271 AC: 4150 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3466

East Asian (EAS) AF: 0.663 AC: 3431 AN: 5178

South Asian (SAS) AF: 0.367 AC: 1768 AN: 4816

European-Finnish (FIN) AF: 0.295 AC: 3101 AN: 10522

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10954 AN: 68006

Other (OTH) AF: 0.193 AC: 408 AN: 2116

Alfa AF: 0.180 Hom.: 3039

Bravo AF: 0.188

Asia WGS AF: 0.490 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.37
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10430719; hg19: chr10-91038981;