10-89357033-A-C

Variant names:

• chr10-89357033-A-C
• rs627524
• NM_001440819.1:c.-2+55758T>G

Variant summary

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

The NM_001440819.1(LIPA):​c.-2+55758T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 151,978 control chromosomes in the GnomAD database, including 32,918 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 0.63 (32918 hom., cov: 31)
• Consequence: LIPA NM_001440819.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 8 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]

IFIT3 (HGNC:5411): (interferon induced protein with tetratricopeptide repeats 3) Enables identical protein binding activity. Involved in negative regulation of apoptotic process; negative regulation of cell population proliferation; and response to virus. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPA	NM_001440819.1	c.-2+55758T>G		intron_variant	Intron 2 of 10		NP_001427748.1
LIPA	NM_001440820.1	c.-2+55708T>G		intron_variant	Intron 2 of 10		NP_001427749.1
LIPA	NM_001440821.1	c.-99+55758T>G		intron_variant	Intron 2 of 11		NP_001427750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPA	ENST00000371837.5	c.61+55758T>G		intron_variant	Intron 2 of 8	2		ENSP00000360903.1
IFIT3	ENST00000679438.1	c.-15-12406A>C		intron_variant	Intron 1 of 3			ENSP00000506015.1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95889 AN: 151860 Hom.: 32866 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.632 AC: 95991 AN: 151978 Hom.: 32918 Cov.: 31 AF XY: 0.634 AC XY: 47052 AN XY: 74264

African (AFR) AF: 0.888 AC: 36828 AN: 41484

American (AMR) AF: 0.583 AC: 8904 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2172 AN: 3472

East Asian (EAS) AF: 0.941 AC: 4869 AN: 5176

South Asian (SAS) AF: 0.587 AC: 2821 AN: 4808

European-Finnish (FIN) AF: 0.493 AC: 5198 AN: 10538

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33103 AN: 67922

Other (OTH) AF: 0.629 AC: 1325 AN: 2108

Alfa AF: 0.500 Hom.: 9428

Bravo AF: 0.648

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs627524; hg19: chr10-91116790;