rs303218

Positions:

• chr10-89392836-G-A
• chr10-89392836-G-C

Variant summary

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

The NM_001548.5(IFIT1):​c.5+119G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,012,666 control chromosomes in the GnomAD database, including 27,805 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 0.19 (3399 hom., cov: 32)
  • Exomes 𝑓: 0.22 (24406 hom.)
• Consequence: IFIT1 NM_001548.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.716

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFIT1	NM_001548.5	c.5+119G>A		intron_variant		ENST00000371804.4	NP_001539.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFIT1	ENST00000371804.4	c.5+119G>A		intron_variant		1	NM_001548.5	ENSP00000360869.3
IFIT1	ENST00000546318.2	c.-324+119G>A		intron_variant		3		ENSP00000441968.1
LIPA	ENST00000371837.5	c.61+19955C>T		intron_variant		2		ENSP00000360903.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28486 AN: 152024 Hom.: 3401 Cov.: 32

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.221 AC: 190040 AN: 860524 Hom.: 24406 AF XY: 0.227 AC XY: 101615 AN XY: 447694

Gnomad4 AFR exome AF: 0.0706

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.187 AC: 28492 AN: 152142 Hom.: 3399 Cov.: 32 AF XY: 0.195 AC XY: 14524 AN XY: 74378

Gnomad4 AFR AF: 0.0766

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.229

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.193

Alfa AF: 0.187 Hom.: 705

Bravo AF: 0.179

Asia WGS AF: 0.364 AC: 1264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.81

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: rs303218; hg19: chr10-91152593; COSMIC: COSV65661362;