rs17468739

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001547.5(IFIT2):c.236A>C(p.Glu79Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,614,066 control chromosomes in the GnomAD database, including 18,962 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. E79D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.11 ( 1290 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17672 hom. )

Consequence

IFIT2
NM_001547.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.508

Publications

27 publications found

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 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

LIPA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018186569).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT2	NM_001547.5 link	c.236A>C	p.Glu79Ala	missense_variant	Exon 2 of 2	ENST00000371826.4	NP_001538.4	P09913Q05DN2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFIT2	ENST00000371826.4 link	c.236A>C	p.Glu79Ala	missense_variant	Exon 2 of 2	1	NM_001547.5	ENSP00000360891.3		P09913

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16597

AN:

152154

Hom.:

1291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0356

Gnomad FIN

AF:

0.0590

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.130

GnomAD2 exomes

AF:

0.112

AC:

28018

AN:

250506

AF XY:

0.113

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.0820

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.0650

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.147

AC:

214704

AN:

1461794

Hom.:

17672

Cov.:

AF XY:

0.144

AC XY:

104884

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0250

AC:

836

AN:

33474

American (AMR)

AF:

0.0872

AC:

3900

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

5544

AN:

26134

East Asian (EAS)

AF:

0.000277

AC:

AN:

39694

South Asian (SAS)

AF:

0.0370

AC:

3195

AN:

86256

European-Finnish (FIN)

AF:

0.0702

AC:

3750

AN:

53412

Middle Eastern (MID)

AF:

0.157

AC:

903

AN:

5768

European-Non Finnish (NFE)

AF:

0.169

AC:

188300

AN:

1111954

Other (OTH)

AF:

0.137

AC:

8265

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

10675

21350

32025

42700

53375

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6382

12764

19146

25528

31910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.109

AC:

16587

AN:

152272

Hom.:

1290

Cov.:

AF XY:

0.103

AC XY:

7654

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0285

AC:

1184

AN:

41552

American (AMR)

AF:

0.120

AC:

1831

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

764

AN:

3468

East Asian (EAS)

AF:

0.00173

AC:

AN:

5190

South Asian (SAS)

AF:

0.0350

AC:

169

AN:

4832

European-Finnish (FIN)

AF:

0.0590

AC:

626

AN:

10614

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.169

AC:

11511

AN:

68008

Other (OTH)

AF:

0.128

AC:

271

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

726

1452

2179

2905

3631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.140

Hom.:

3571

Bravo

AF:

0.112

TwinsUK

AF:

0.163

AC:

605

ALSPAC

AF:

0.163

AC:

628

ESP6500AA

AF:

0.0361

AC:

159

ESP6500EA

AF:

0.172

AC:

1483

ExAC

AF:

0.112

AC:

13623

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.180

EpiControl

AF:

0.175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.70

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.41

T;T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.48

.;T;T

MetaRNN

Benign

0.0018

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.

PhyloP100

0.51

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.8

.;D;.

REVEL

Benign

0.16

Sift

Benign

0.12

.;T;.

Sift4G

Benign

0.11

.;T;T

Polyphen

0.032

B;B;.

Vest4

0.071, 0.057

MPC

0.20

ClinPred

0.0077

GERP RS

-2.1

PromoterAI

0.021

Neutral

(source)

Varity_R

0.17

gMVP

0.32

Mutation Taster

=92/8

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over