10-89399566-G-T

Variant names:

• chr10-89399566-G-T
• rs304484
• NM_001548.5:c.6-2715G>T

Variant summary

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

The NM_001548.5(IFIT1):​c.6-2715G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 151,794 control chromosomes in the GnomAD database, including 9,577 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 0.34 (9577 hom., cov: 32)
• Consequence: IFIT1 NM_001548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521
• Publications: 5 publications found

Genes affected

IFIT1 (HGNC:5407): (interferon induced protein with tetratricopeptide repeats 1) This gene encodes a protein containing tetratricopeptide repeats that was originally identified as induced upon treatment with interferon. The encoded protein may inhibit viral replication and translational initiation. This gene is located in a cluster on chromosome 10 with five other closely related genes. There is a pseudogene for this gene on chromosome 13. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2012]

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT1	NM_001548.5	c.6-2715G>T		intron_variant	Intron 1 of 1	ENST00000371804.4	NP_001539.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFIT1	ENST00000371804.4	c.6-2715G>T		intron_variant	Intron 1 of 1	1	NM_001548.5	ENSP00000360869.3
IFIT1	ENST00000546318.2	c.-88-2715G>T		intron_variant	Intron 2 of 2	3		ENSP00000441968.1
LIPA	ENST00000371837.5	c.61+13225C>A		intron_variant	Intron 2 of 8	2		ENSP00000360903.1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51145 AN: 151676 Hom.: 9565 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.337 AC: 51197 AN: 151794 Hom.: 9577 Cov.: 32 AF XY: 0.344 AC XY: 25535 AN XY: 74188

African (AFR) AF: 0.461 AC: 19059 AN: 41332

American (AMR) AF: 0.324 AC: 4944 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1177 AN: 3464

East Asian (EAS) AF: 0.610 AC: 3154 AN: 5168

South Asian (SAS) AF: 0.486 AC: 2341 AN: 4812

European-Finnish (FIN) AF: 0.295 AC: 3098 AN: 10504

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16359 AN: 67938

Other (OTH) AF: 0.330 AC: 692 AN: 2098

Alfa AF: 0.136 Hom.: 208

Bravo AF: 0.338

Asia WGS AF: 0.509 AC: 1767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		0.52
Mutation Taster		=297/3	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: rs304484; hg19: chr10-91159323;