Genetic Variant IFI44L:p.Tyr291* (chr1-78635486-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_006820.4(IFI44L):c.873T>A(p.Tyr291*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,610,308 control chromosomes in the GnomAD database, including 38 homozygotes. Variant has been reported in ClinVar as risk factor (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0047 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 35 hom. )

Consequence

IFI44L
NM_006820.4 stop_gained

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -1.51

Variant links:

Genes affected

IFI44L (HGNC:17817): (interferon induced protein 44 like) Predicted to enable GTP binding activity. Involved in defense response to virus. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IFI44L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI44L	NM_006820.4 link	c.873T>A	p.Tyr291*	stop_gained	Exon 5 of 9	ENST00000370751.10	NP_006811.2	Q53G44-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI44L	ENST00000370751.10 link	c.873T>A	p.Tyr291*	stop_gained	Exon 5 of 9	1	NM_006820.4	ENSP00000359787.4		Q53G44-1
IFI44L	ENST00000459784.6 link	c.99T>A	p.Tyr33*	stop_gained	Exon 5 of 9	3		ENSP00000506096.1		B4E019

Frequencies

GnomAD3 genomes

AF:

0.00474

AC:

721

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00622

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00759

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00532

AC:

1312

AN:

246634

AF XY:

0.00559

show subpopulations

Gnomad AFR exome

AF:

0.000988

Gnomad AMR exome

AF:

0.00352

Gnomad ASJ exome

AF:

0.0117

Gnomad EAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00514

Gnomad NFE exome

AF:

0.00768

Gnomad OTH exome

AF:

0.00365

GnomAD4 exome

AF:

0.00663

AC:

9664

AN:

1458076

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

4712

AN XY:

725198

show subpopulations

Gnomad4 AFR exome

AF:

0.000930

AC:

AN:

33326

Gnomad4 AMR exome

AF:

0.00340

AC:

149

AN:

43800

Gnomad4 ASJ exome

AF:

0.0107

AC:

279

AN:

26024

Gnomad4 EAS exome

AF:

0.000101

AC:

AN:

39620

Gnomad4 SAS exome

AF:

0.00213

AC:

181

AN:

85176

Gnomad4 FIN exome

AF:

0.00519

AC:

277

AN:

53396

Gnomad4 NFE exome

AF:

0.00752

AC:

8355

AN:

1110720

Gnomad4 Remaining exome

AF:

0.00582

AC:

351

AN:

60266

Heterozygous variant carriers

436

873

1309

1746

2182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.00473

AC:

720

AN:

152232

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00125

AC:

0.00125126

AN:

0.00125126

Gnomad4 AMR

AF:

0.00249

AC:

0.00248626

AN:

0.00248626

Gnomad4 ASJ

AF:

0.00807

AC:

0.00807382

AN:

0.00807382

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00145

AC:

0.00144868

AN:

0.00144868

Gnomad4 FIN

AF:

0.00622

AC:

0.00622055

AN:

0.00622055

Gnomad4 NFE

AF:

0.00758

AC:

0.0075762

AN:

0.0075762

Gnomad4 OTH

AF:

0.00426

AC:

0.00426136

AN:

0.00426136

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

100

<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:

0.00697

Hom.:

Bravo

AF:

0.00448

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00791

AC:

ExAC

AF:

0.00530

AC:

643

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00769

EpiControl

AF:

0.00890

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Multisystem inflammatory syndrome in children

Other:1

Nov 14, 2021

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.45

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

-0.049

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.30

Vest4

0.84

GERP RS

-2.2

Mutation Taster

=155/45

disease causing (fs/PTC)

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over