rs954439

chr10-89306703-T-Achr10-89306703-T-Cchr10-89306703-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001547.5(IFIT2):c.747T>A(p.Val249=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

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]

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 -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/exons	MANE	UniProt
IFIT2	NM_001547.5	c.747T>A	p.Val249=	synonymous_variant	2/2	ENST00000371826.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFIT2	ENST00000371826.4	c.747T>A	p.Val249=	synonymous_variant	2/2	1	NM_001547.5	P1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91134 AN: 151984 Hom.: 29277 Cov.: 32

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

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.: 55 AF XY: 0.498 AC XY: 362339 AN XY: 727140

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.: 32 AF XY: 0.600 AC XY: 44620 AN XY: 74372

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

Other links and lift over

dbSNP: rs954439; hg19: chr10-91066460;