dbSNP rs954439: IFIT2:p.Val249Val (chr10-89306703-T-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001547.5(IFIT2):c.747T>A(p.Val249Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,613,766 control chromosomes in the GnomAD database, including 216,205 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 0.60 ( 29313 hom., cov: 32)

Exomes 𝑓: 0.50 ( 186892 hom. )

Consequence

IFIT2
NM_001547.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.533

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-0.533 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFIT2	NM_001547.5 link	c.747T>A	p.Val249Val	synonymous_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.747T>A	p.Val249Val	synonymous_variant	Exon 2 of 2	1	NM_001547.5	ENSP00000360891.3		P09913

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91134

AN:

151984

Hom.:

29277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.825

Gnomad AMI

AF:

0.621

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.864

Gnomad SAS

AF:

0.554

Gnomad FIN

AF:

0.464

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.478

Gnomad OTH

AF:

0.599

GnomAD3 exomes

AF:

0.552

AC:

137605

AN:

249424

Hom.:

39975

AF XY:

0.544

AC XY:

73587

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.836

Gnomad AMR exome

AF:

0.536

Gnomad ASJ exome

AF:

0.557

Gnomad EAS exome

AF:

0.877

Gnomad SAS exome

AF:

0.548

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.484

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.498

AC:

727884

AN:

1461664

Hom.:

186892

Cov.:

AF XY:

0.498

AC XY:

362339

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.837

Gnomad4 AMR exome

AF:

0.536

Gnomad4 ASJ exome

AF:

0.565

Gnomad4 EAS exome

AF:

0.843

Gnomad4 SAS exome

AF:

0.543

Gnomad4 FIN exome

AF:

0.469

Gnomad4 NFE exome

AF:

0.468

Gnomad4 OTH exome

AF:

0.532

GnomAD4 genome

AF:

0.600

AC:

91218

AN:

152102

Hom.:

29313

Cov.:

AF XY:

0.600

AC XY:

44620

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.825

Gnomad4 AMR

AF:

0.554

Gnomad4 ASJ

AF:

0.570

Gnomad4 EAS

AF:

0.864

Gnomad4 SAS

AF:

0.554

Gnomad4 FIN

AF:

0.464

Gnomad4 NFE

AF:

0.478

Gnomad4 OTH

AF:

0.602

Alfa

AF:

0.514

Hom.:

6850

Bravo

AF:

0.615

Asia WGS

AF:

0.698

AC:

2423

AN:

3478

EpiCase

AF:

0.491

EpiControl

AF:

0.484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.42

DANN

Benign

0.84

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

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