chr10-89363067-T-G

Position:

• chr10-89363067-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000371837.5(LIPA):​c.61+49724A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 226,380 control chromosomes in the GnomAD database, including 45,235 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 (32979 hom., cov: 32)
  • Exomes 𝑓: 0.56 (12256 hom.)
• Consequence: LIPA ENST00000371837.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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]

IFIT6P (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT6P		n.89363067T>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPA	ENST00000371837.5	c.61+49724A>C		intron_variant		2		ENSP00000360903.1
IFIT3	ENST00000679438.1	c.-15-6372T>G		intron_variant				ENSP00000506015.1
IFIT6P	ENST00000418257.1	n.774T>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96036 AN: 152008 Hom.: 32928 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.564 AC: 41857 AN: 74254 Hom.: 12256 Cov.: 0 AF XY: 0.554 AC XY: 23787 AN XY: 42930

Gnomad4 AFR exome AF: 0.900

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.649

Gnomad4 EAS exome AF: 0.936

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.506

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.632 AC: 96137 AN: 152126 Hom.: 32979 Cov.: 32 AF XY: 0.634 AC XY: 47153 AN XY: 74382

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.940

Gnomad4 SAS AF: 0.588

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.631

Alfa AF: 0.367 Hom.: 835

Bravo AF: 0.648

Asia WGS AF: 0.741 AC: 2571 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs305375; hg19: chr10-91122824;