rs11594137

Variant names:

• chr10-89215450-A-C
• rs11594137
• NM_000235.4:c.967-389T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-89215450-A-C
• chr10-89215450-A-T

Variant summary

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

The NM_000235.4(LIPA):​c.967-389T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,250 control chromosomes in the GnomAD database, including 1,038 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 0.11 (1038 hom., cov: 32)
• Consequence: LIPA NM_000235.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPA	NM_000235.4	c.967-389T>G		intron_variant	Intron 9 of 9	ENST00000336233.10	NP_000226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPA	ENST00000336233.10	c.967-389T>G		intron_variant	Intron 9 of 9	1	NM_000235.4	ENSP00000337354.5
LIPA	ENST00000371837.5	c.799-389T>G		intron_variant	Intron 8 of 8	2		ENSP00000360903.1
LIPA	ENST00000456827.5	c.619-389T>G		intron_variant	Intron 7 of 7	3		ENSP00000413019.2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16547 AN: 152132 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0544

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.0912

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.0988

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

GnomAD4 genome AF: 0.109 AC: 16552 AN: 152250 Hom.: 1038 Cov.: 32 AF XY: 0.107 AC XY: 7947 AN XY: 74428

African (AFR) AF: 0.0811 AC: 3369 AN: 41544

American (AMR) AF: 0.0750 AC: 1148 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0544 AC: 189 AN: 3472

East Asian (EAS) AF: 0.0268 AC: 139 AN: 5186

South Asian (SAS) AF: 0.0902 AC: 435 AN: 4822

European-Finnish (FIN) AF: 0.128 AC: 1356 AN: 10588

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.140 AC: 9542 AN: 68028

Other (OTH) AF: 0.0991 AC: 209 AN: 2108

Alfa AF: 0.126 Hom.: 4356

Bravo AF: 0.104

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.67
PhyloP100		0.056
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: rs11594137; hg19: chr10-90975207;