chr10-89243170-C-T

Variant names:

• chr10-89243170-C-T
• rs1412444
• NM_000235.4:c.229+2506G>A

Variant summary

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

The NM_000235.4(LIPA):​c.229+2506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,990 control chromosomes in the GnomAD database, including 10,734 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 0.37 (10734 hom., cov: 32)
• Consequence: LIPA NM_000235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 136 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000235.4. 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_000235.4	MANE Select	c.229+2506G>A		intron	N/A	NP_000226.2	P38571-1
	LIPA	NM_001440836.1		c.361+2506G>A		intron	N/A	NP_001427765.1
	LIPA	NM_001440837.1		c.229+2506G>A		intron	N/A	NP_001427766.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPA	ENST00000336233.10	TSL:1 MANE Select	c.229+2506G>A		intron	N/A	ENSP00000337354.5	P38571-1
	LIPA	ENST00000428800.5	TSL:1	c.229+2506G>A		intron	N/A	ENSP00000388415.1	Q5T073
	LIPA	ENST00000868683.1		c.229+2506G>A		intron	N/A	ENSP00000538742.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56281 AN: 151870 Hom.: 10709 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.371 AC: 56352 AN: 151990 Hom.: 10734 Cov.: 32 AF XY: 0.374 AC XY: 27784 AN XY: 74290

African (AFR) AF: 0.390 AC: 16165 AN: 41456

American (AMR) AF: 0.428 AC: 6541 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3470

East Asian (EAS) AF: 0.313 AC: 1619 AN: 5168

South Asian (SAS) AF: 0.525 AC: 2530 AN: 4818

European-Finnish (FIN) AF: 0.403 AC: 4250 AN: 10544

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.338 AC: 22940 AN: 67938

Other (OTH) AF: 0.371 AC: 783 AN: 2108

Alfa AF: 0.348 Hom.: 37522

Bravo AF: 0.371

Asia WGS AF: 0.475 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1412444; hg19: chr10-91002927;