Variant rs2070845 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001547.5(IFIT2):c.362A>G(p.Lys121Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,760 control chromosomes in the GnomAD database, including 44,174 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.24 ( 4501 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39673 hom. )

Consequence

IFIT2
NM_001547.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

IFIT2 (HGNC:5409): (interferon induced protein with tetratricopeptide repeats 2) Enables RNA binding activity. Involved in negative regulation of protein binding activity; positive regulation of apoptotic process; and response to virus. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

IFIT2 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033346713).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFIT2	NM_001547.5 linkuse as main transcript	c.362A>G	p.Lys121Arg	missense_variant	2/2	ENST00000371826.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFIT2	ENST00000371826.4 linkuse as main transcript	c.362A>G	p.Lys121Arg	missense_variant	2/2	1	NM_001547.5	P1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36334

AN:

151962

Hom.:

4501

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.379

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.252

GnomAD3 exomes

AF:

0.212

AC:

52847

AN:

249812

Hom.:

6068

AF XY:

0.207

AC XY:

28098

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.266

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.246

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.229

AC:

335431

AN:

1461680

Hom.:

39673

Cov.:

AF XY:

0.226

AC XY:

164273

AN XY:

727154

show subpopulations

Gnomad4 AFR exome

AF:

0.259

Gnomad4 AMR exome

AF:

0.198

Gnomad4 ASJ exome

AF:

0.266

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.242

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.239

AC:

36343

AN:

152080

Hom.:

4501

Cov.:

AF XY:

0.234

AC XY:

17412

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.266

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.270

Gnomad4 EAS

AF:

0.128

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.244

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.243

Hom.:

9513

Bravo

AF:

0.246

TwinsUK

AF:

0.232

AC:

861

ALSPAC

AF:

0.239

AC:

921

ESP6500AA

AF:

0.251

AC:

1062

ESP6500EA

AF:

0.242

AC:

2063

ExAC

AF:

0.214

AC:

25933

Asia WGS

AF:

0.140

AC:

485

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

Cadd

Benign

5.6

Dann

Benign

0.79

DEOGEN2

Benign

0.033

T;T;.

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.65

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.70

N;N;.

MutationTaster

Benign

0.0000032

P;P;P;P;P

PrimateAI

Benign

0.27

Polyphen

0.028

B;B;.

Vest4

0.024, 0.015

MPC

0.15

ClinPred

0.00058

GERP RS

2.2

Varity_R

0.081

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over