NM_000235.4:c.230-4049C>G

Variant names:

• chr10-89232447-G-C
• rs951647
• NM_000235.4:c.230-4049C>G

Variant summary

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

The NM_000235.4(LIPA):​c.230-4049C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 152,134 control chromosomes in the GnomAD database, including 11,221 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 0.38 (11221 hom., cov: 33)
• Consequence: LIPA NM_000235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 3 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, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
• 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 (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPA	NM_000235.4	c.230-4049C>G		intron_variant	Intron 3 of 9	ENST00000336233.10	NP_000226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPA	ENST00000336233.10	c.230-4049C>G		intron_variant	Intron 3 of 9	1	NM_000235.4	ENSP00000337354.5

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57049 AN: 152016 Hom.: 11227 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.375 AC: 57054 AN: 152134 Hom.: 11221 Cov.: 33 AF XY: 0.376 AC XY: 27970 AN XY: 74368

African (AFR) AF: 0.249 AC: 10350 AN: 41510

American (AMR) AF: 0.361 AC: 5526 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 1441 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1871 AN: 5176

South Asian (SAS) AF: 0.353 AC: 1703 AN: 4818

European-Finnish (FIN) AF: 0.440 AC: 4648 AN: 10560

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30249 AN: 67982

Other (OTH) AF: 0.368 AC: 778 AN: 2114

Alfa AF: 0.413 Hom.: 1672

Bravo AF: 0.360

Asia WGS AF: 0.318 AC: 1104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.77
PhyloP100		0.037
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: rs951647; hg19: chr10-90992204;