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GeneBe

rs1990760

Variant summary

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

The NM_022168(IFIH1):c.2836G>A(p.Ala946Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 151970 control chromosomes in the gnomAD Genomes database, including 18242 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (β˜…β˜…).

Frequency

Genomes: 𝑓 0.45 ( 18242 hom., cov: 33)
Exomes 𝑓: 0.50 ( 34569 hom. )

Consequence

IFIH1
NM_022168 missense

Scores

13

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.750

Links

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
?
Computational evidence support a benign effect (MetaRNN=2.7895177E-5).
BP6
?
Variant 2:162267541-C>T is Benign according to our data. Variant chr2-162267541-C-T is described in ClinVar as [Benign]. Clinvar id is 261566. Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IFIH1NM_022168.4 linkuse as main transcriptc.2836G>A p.Ala946Thr missense_variant 15/16 ENST00000649979.2
IFIH1XM_047445407.1 linkuse as main transcriptc.2119G>A p.Ala707Thr missense_variant 14/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IFIH1ENST00000649979.2 linkuse as main transcriptc.2836G>A p.Ala946Thr missense_variant 15/16 NM_022168.4 P1Q9BYX4-1

Frequencies

GnomAD3 genomes
AF:
0.452
AC:
68651
AN:
151970
Hom.:
18242
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.186
Gnomad AMI
AF:
0.574
Gnomad AMR
AF:
0.443
Gnomad ASJ
AF:
0.462
Gnomad EAS
AF:
0.195
Gnomad SAS
AF:
0.514
Gnomad FIN
AF:
0.568
Gnomad MID
AF:
0.491
Gnomad NFE
AF:
0.610
Gnomad OTH
AF:
0.471
GnomAD3 exomes
AF:
0.502
AC:
125999
AN:
251196
Hom.:
34569
AF XY:
0.515
AC XY:
69974
AN XY:
135774
show subpopulations
Gnomad AFR exome
AF:
0.175
Gnomad AMR exome
AF:
0.424
Gnomad ASJ exome
AF:
0.454
Gnomad EAS exome
AF:
0.174
Gnomad SAS exome
AF:
0.533
Gnomad FIN exome
AF:
0.572
Gnomad NFE exome
AF:
0.606
Gnomad OTH exome
AF:
0.529
GnomAD4 exome
AF:
0.569
AC:
830046
AN:
1457798
Hom.:
244347
AF XY:
0.570
AC XY:
413369
AN XY:
725498
show subpopulations
Gnomad4 AFR exome
AF:
0.166
Gnomad4 AMR exome
AF:
0.426
Gnomad4 ASJ exome
AF:
0.452
Gnomad4 EAS exome
AF:
0.202
Gnomad4 SAS exome
AF:
0.529
Gnomad4 FIN exome
AF:
0.575
Gnomad4 NFE exome
AF:
0.609
Gnomad4 OTH exome
AF:
0.529
Alfa
AF:
0.563
Hom.:
62070
Bravo
AF:
0.424
TwinsUK
AF:
0.598
AC:
2217
ALSPAC
AF:
0.605
AC:
2330
ESP6500AA
AF:
0.185
AC:
816
ESP6500EA
AF:
0.603
AC:
5185
ExAC
AF:
0.505
AC:
61267
Asia WGS
AF:
0.326
AC:
1136
AN:
3478
EpiCase
AF:
0.596
EpiControl
AF:
0.586

ClinVar

Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, PreventionGenetics-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 12, 2018This variant is associated with the following publications: (PMID: 31866997, 22561518, 28553952, 28973304, 23441136, 27720759, 28000722, 23734776, 16699517, 24386202, 20644636, 20694011, 20467774, 17535987, 19324880, 21705624, 19539001, 18927125, 19841890, 24117221, 24995871) -
Aicardi-Goutieres syndrome 7 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -
Aicardi-Goutieres syndrome 7;C4225427:Singleton-Merten syndrome 1 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 04, 2022- -
Singleton-Merten syndrome 1 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.71
T
BayesDel_noAF
Benign
-0.65
Cadd
Benign
9.2
Dann
Benign
0.76
DEOGEN2
Benign
0.028
T;T;.
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.64
D
MetaRNN
Benign
0.000028
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.6
L;L;.
MutationTaster
Benign
0.21
P;P
PrimateAI
Benign
0.29
T
Polyphen
0.10
B;B;.
Vest4
0.017
MPC
0.024
ClinPred
0.0023
T
GERP RS
3.9
Varity_R
0.075
gMVP
0.23

Splicing

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.

Other links and lift over

dbSNP: rs1990760; hg19: chr2-163124051; COSMIC: COSV55125663;