rs10509571

Variant names:

• chr10-89332801-T-A
• rs10509571
• NM_001549.6:c.5+4723T>A

Variant summary

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

The NM_001549.6(IFIT3):​c.5+4723T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,014 control chromosomes in the GnomAD database, including 5,717 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 0.27 (5717 hom., cov: 32)
• Consequence: IFIT3 NM_001549.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.397
• Publications: 4 publications found

Genes affected

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]

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]

LIPA Gene-Disease associations (from GenCC):

• lysosomal acid lipase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen, Myriad Women’s Health, Labcorp Genetics (formerly Invitae)
• cholesteryl ester storage disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Wolman disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001549.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFIT3	NM_001549.6	MANE Select	c.5+4723T>A		intron	N/A	NP_001540.2
	IFIT3	NM_001031683.4		c.5+174T>A		intron	N/A	NP_001026853.1
	LIPA	NM_001440836.1		c.14+9760A>T		intron	N/A	NP_001427765.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFIT3	ENST00000371818.9	TSL:1 MANE Select	c.5+4723T>A		intron	N/A	ENSP00000360883.4
	IFIT3	ENST00000371811.4	TSL:1	c.5+174T>A		intron	N/A	ENSP00000360876.4
	LIPA	ENST00000487618.5	TSL:1	n.64+9810A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40486 AN: 151896 Hom.: 5719 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.266 AC: 40505 AN: 152014 Hom.: 5717 Cov.: 32 AF XY: 0.263 AC XY: 19538 AN XY: 74306

African (AFR) AF: 0.325 AC: 13459 AN: 41430

American (AMR) AF: 0.251 AC: 3830 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1090 AN: 3472

East Asian (EAS) AF: 0.324 AC: 1674 AN: 5164

South Asian (SAS) AF: 0.121 AC: 586 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2101 AN: 10550

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.246 AC: 16700 AN: 67980

Other (OTH) AF: 0.273 AC: 577 AN: 2112

Alfa AF: 0.249 Hom.: 628

Bravo AF: 0.277

Asia WGS AF: 0.236 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.7
DANN	Benign	0.82
PhyloP100		-0.40
PromoterAI		0.00070	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10509571; hg19: chr10-91092558;