10-89245129-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000235.4(LIPA):​c.229+547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,042 control chromosomes in the GnomAD database, including 11,539 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 ( 11539 hom., cov: 33)

Consequence

LIPA
NM_000235.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.866
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LIPANM_000235.4 linkc.229+547T>C intron_variant ENST00000336233.10 NP_000226.2 P38571-1
LIPANM_001127605.3 linkc.229+547T>C intron_variant NP_001121077.1 P38571-1
LIPANM_001288979.2 linkc.-120+6608T>C intron_variant NP_001275908.1 P38571A0A0A0MT32
LIPAXM_024448023.2 linkc.229+547T>C intron_variant XP_024303791.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LIPAENST00000336233.10 linkc.229+547T>C intron_variant 1 NM_000235.4 ENSP00000337354.5 P38571-1

Frequencies

GnomAD3 genomes
AF:
0.384
AC:
58355
AN:
151924
Hom.:
11509
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.423
Gnomad AMI
AF:
0.160
Gnomad AMR
AF:
0.430
Gnomad ASJ
AF:
0.362
Gnomad EAS
AF:
0.337
Gnomad SAS
AF:
0.527
Gnomad FIN
AF:
0.408
Gnomad MID
AF:
0.427
Gnomad NFE
AF:
0.344
Gnomad OTH
AF:
0.379
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.384
AC:
58429
AN:
152042
Hom.:
11539
Cov.:
33
AF XY:
0.387
AC XY:
28748
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.423
Gnomad4 AMR
AF:
0.432
Gnomad4 ASJ
AF:
0.362
Gnomad4 EAS
AF:
0.336
Gnomad4 SAS
AF:
0.526
Gnomad4 FIN
AF:
0.408
Gnomad4 NFE
AF:
0.344
Gnomad4 OTH
AF:
0.378
Alfa
AF:
0.326
Hom.:
5437
Bravo
AF:
0.386
Asia WGS
AF:
0.480
AC:
1667
AN:
3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
7.4
DANN
Benign
0.59

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2246942; hg19: chr10-91004886; API