rs303218

Variant names:

• chr10-89392836-G-A
• rs303218
• NM_001548.5:c.5+119G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001548.5. 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
	IFIT1	NM_001548.5	MANE Select	c.5+119G>A		intron	N/A	NP_001539.3
	IFIT1	NM_001270927.2		c.-93+119G>A		intron	N/A	NP_001257856.1
	IFIT1	NM_001270928.2		c.-203+119G>A		intron	N/A	NP_001257857.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFIT1	ENST00000371804.4	TSL:1 MANE Select	c.5+119G>A		intron	N/A	ENSP00000360869.3
	IFIT1	ENST00000546318.2	TSL:3	c.-324+119G>A		intron	N/A	ENSP00000441968.1
	LIPA	ENST00000371837.5	TSL:2	c.61+19955C>T		intron	N/A	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

African (AFR) AF: 0.0706 AC: 1504 AN: 21310

American (AMR) AF: 0.292 AC: 10889 AN: 37238

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 5756 AN: 20976

East Asian (EAS) AF: 0.503 AC: 17610 AN: 35008

South Asian (SAS) AF: 0.361 AC: 24933 AN: 69100

European-Finnish (FIN) AF: 0.216 AC: 10555 AN: 48886

Middle Eastern (MID) AF: 0.252 AC: 841 AN: 3342

European-Non Finnish (NFE) AF: 0.187 AC: 109001 AN: 584400

Other (OTH) AF: 0.222 AC: 8951 AN: 40264

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

African (AFR) AF: 0.0766 AC: 3182 AN: 41540

American (AMR) AF: 0.247 AC: 3772 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3468

East Asian (EAS) AF: 0.539 AC: 2784 AN: 5168

South Asian (SAS) AF: 0.352 AC: 1697 AN: 4818

European-Finnish (FIN) AF: 0.229 AC: 2418 AN: 10564

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13037 AN: 67986

Other (OTH) AF: 0.193 AC: 407 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.81
PhyloP100		-0.72
PromoterAI		-0.016	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: rs303218; hg19: chr10-91152593; COSMIC: COSV65661362;