10-89357033-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001440819.1(LIPA):​c.-2+55758T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 152,034 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00028 (0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPA	NM_001440819.1	c.-2+55758T>A		intron_variant	Intron 2 of 10		NP_001427748.1
LIPA	NM_001440820.1	c.-2+55708T>A		intron_variant	Intron 2 of 10		NP_001427749.1
LIPA	NM_001440821.1	c.-99+55758T>A		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>A		intron_variant	Intron 2 of 8	2		ENSP00000360903.1
IFIT3	ENST00000679438.1	c.-15-12406A>T		intron_variant	Intron 1 of 3			ENSP00000506015.1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 151916 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.000283 AC: 43 AN: 152034 Hom.: 0 Cov.: 31 AF XY: 0.000256 AC XY: 19 AN XY: 74294

African (AFR) AF: 0.0000723 AC: 3 AN: 41492

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000545 AC: 37 AN: 67948

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 9428

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.5
DANN	Benign	0.16
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism

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;