10-89243170-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPA	NM_000235.4	c.229+2506G>A		intron_variant	Intron 3 of 9	ENST00000336233.10	NP_000226.2
LIPA	NM_001127605.3	c.229+2506G>A		intron_variant	Intron 3 of 9		NP_001121077.1
LIPA	NM_001288979.2	c.-120+8567G>A		intron_variant	Intron 1 of 7		NP_001275908.1
LIPA	XM_024448023.2	c.229+2506G>A		intron_variant	Intron 3 of 9		XP_024303791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPA	ENST00000336233.10	c.229+2506G>A		intron_variant	Intron 3 of 9	1	NM_000235.4	ENSP00000337354.5

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

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.371

Alfa AF: 0.347 Hom.: 18528

Bravo AF: 0.371

Asia WGS AF: 0.475 AC: 1652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs1412444; hg19: chr10-91002927;