Variant 1-78628357-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006820.4(IFI44L):c.442C>T(p.Arg148Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,585,476 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R148H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.015 ( 60 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 41 hom. )

Consequence

IFI44L
NM_006820.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.43

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025875866).

BP6

Variant 1-78628357-C-T is Benign according to our data. Variant chr1-78628357-C-T is described in ClinVar as [Benign]. Clinvar id is 786463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI44L	NM_006820.4 linkuse as main transcript	c.442C>T	p.Arg148Cys	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.442C>T	p.Arg148Cys	missense_variant	2/9	1	NM_006820.4	P1	Q53G44-1

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2337

AN:

151868

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00499

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000177

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00397

AC:

914

AN:

230380

Hom.:

AF XY:

0.00301

AC XY:

376

AN XY:

124944

show subpopulations

Gnomad AFR exome

AF:

0.0562

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000192

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000559

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00145

AC:

2075

AN:

1433490

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

876

AN XY:

712044

show subpopulations

Gnomad4 AFR exome

AF:

0.0541

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000673

Gnomad4 OTH exome

AF:

0.00319

GnomAD4 genome

AF:

0.0154

AC:

2339

AN:

151986

Hom.:

Cov.:

AF XY:

0.0141

AC XY:

1048

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0538

Gnomad4 AMR

AF:

0.00499

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000177

Gnomad4 OTH

AF:

0.00711

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.0174

ESP6500AA

AF:

0.0463

AC:

203

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00490

AC:

594

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000594

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

0.14

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.052

DANN

Benign

0.68

DEOGEN2

Benign

0.00062

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.39

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.33

N;N

REVEL

Benign

0.014

Sift

Benign

0.17

T;T

Sift4G

Benign

0.070

T;T

Polyphen

0.030

B;.

Vest4

0.13

MVP

0.11

MPC

0.014

ClinPred

0.0016

GERP RS

-6.0

Varity_R

0.095

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

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