rs304485

Variant names:

• chr10-89400153-T-A
• rs304485
• NM_001548.5:c.6-2128T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-89400153-T-A
• chr10-89400153-T-G

Variant summary

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

The NM_001548.5(IFIT1):​c.6-2128T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,118 control chromosomes in the GnomAD database, including 32,851 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 0.64 (32851 hom., cov: 32)
• Consequence: IFIT1 NM_001548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT1	NM_001548.5	c.6-2128T>A		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.6-2128T>A		intron_variant	Intron 1 of 1	1	NM_001548.5	ENSP00000360869.3
IFIT1	ENST00000546318.2	c.-88-2128T>A		intron_variant	Intron 2 of 2	3		ENSP00000441968.1
LIPA	ENST00000371837.5	c.61+12638A>T		intron_variant	Intron 2 of 8	2		ENSP00000360903.1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96558 AN: 152000 Hom.: 32808 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.792

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.635 AC: 96652 AN: 152118 Hom.: 32851 Cov.: 32 AF XY: 0.637 AC XY: 47350 AN XY: 74358

African (AFR) AF: 0.876 AC: 36407 AN: 41538

American (AMR) AF: 0.589 AC: 8996 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2142 AN: 3472

East Asian (EAS) AF: 0.846 AC: 4380 AN: 5178

South Asian (SAS) AF: 0.587 AC: 2827 AN: 4820

European-Finnish (FIN) AF: 0.510 AC: 5379 AN: 10552

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34303 AN: 67958

Other (OTH) AF: 0.629 AC: 1330 AN: 2114

Alfa AF: 0.378 Hom.: 876

Bravo AF: 0.655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.70
DANN	Benign	0.30
PhyloP100		-0.55
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: rs304485; hg19: chr10-91159910;