Variant chr1-78628091-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006820.4(IFI44L):c.176A>G(p.Asn59Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,613,112 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 5 hom. )

Consequence

IFI44L
NM_006820.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.32

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042441785).

BP6

Variant 1-78628091-A-G is Benign according to our data. Variant chr1-78628091-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 790335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI44L	NM_006820.4 linkuse as main transcript	c.176A>G	p.Asn59Ser	missense_variant	2/9	ENST00000370751.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI44L	ENST00000370751.10 linkuse as main transcript	c.176A>G	p.Asn59Ser	missense_variant	2/9	1	NM_006820.4	P1	Q53G44-1

Frequencies

GnomAD3 genomes

AF:

0.00226

AC:

344

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.000722

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00313

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00157

AC:

393

AN:

249940

Hom.:

AF XY:

0.00150

AC XY:

202

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.000756

Gnomad ASJ exome

AF:

0.000797

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.00297

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.00294

AC:

4292

AN:

1460884

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

2044

AN XY:

726732

show subpopulations

Gnomad4 AFR exome

AF:

0.000538

Gnomad4 AMR exome

AF:

0.000941

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000221

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00359

Gnomad4 OTH exome

AF:

0.00280

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152228

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000722

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00312

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00260

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00337

AC:

ExAC

AF:

0.00156

AC:

189

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00374

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.0010

DANN

Benign

0.14

DEOGEN2

Benign

0.0016

.;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.56

T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

.;L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.058

Sift

Benign

0.60

T;T;T

Sift4G

Benign

0.90

T;T;T

Polyphen

0.0050

.;B;.

Vest4

0.070

MVP

0.085

MPC

0.013

ClinPred

0.0026

GERP RS

-6.0

Varity_R

0.018

gMVP

0.071

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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