rs304485

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IFIT1	NM_001548.5	c.6-2128T>A		intron_variant		ENST00000371804.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFIT1	ENST00000371804.4	c.6-2128T>A		intron_variant		1	NM_001548.5	P1
LIPA	ENST00000371837.5	c.61+12638A>T		intron_variant		2
IFIT1	ENST00000546318.2	c.-88-2128T>A		intron_variant		3

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

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.846

Gnomad4 SAS AF: 0.587

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.629

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs304485; hg19: chr10-91159910;