7-112462016-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001550.4(IFRD1):ā€‹c.634C>Gā€‹(p.Leu212Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,612,418 control chromosomes in the GnomAD database, including 66 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 (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0026 ( 9 hom., cov: 32)
Exomes š‘“: 0.0018 ( 57 hom. )

Consequence

IFRD1
NM_001550.4 missense

Scores

2
16

Clinical Significance

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

Conservation

PhyloP100: 2.48
Variant links:
Genes affected
IFRD1 (HGNC:5456): (interferon related developmental regulator 1) This gene is an immediate early gene that encodes a protein related to interferon-gamma. This protein may function as a transcriptional co-activator/repressor that controls the growth and differentiation of specific cell types during embryonic development and tissue regeneration. Mutations in this gene are associated with sensory/motor neuropathy with ataxia. This gene may also be involved in modulating the pathogenesis of cystic fibrosis lung disease. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

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=0.0065864623).
BP6
Variant 7-112462016-C-G is Benign according to our data. Variant chr7-112462016-C-G is described in ClinVar as [Benign]. Clinvar id is 218480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-112462016-C-G is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00177 (2591/1460266) while in subpopulation AMR AF= 0.0406 (1813/44654). AF 95% confidence interval is 0.039. There are 57 homozygotes in gnomad4_exome. There are 1111 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IFRD1NM_001550.4 linkuse as main transcriptc.634C>G p.Leu212Val missense_variant 7/12 ENST00000403825.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IFRD1ENST00000403825.8 linkuse as main transcriptc.634C>G p.Leu212Val missense_variant 7/121 NM_001550.4 P3O00458-1

Frequencies

GnomAD3 genomes
AF:
0.00258
AC:
392
AN:
152034
Hom.:
8
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00135
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0159
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00424
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00397
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00720
AC:
1805
AN:
250656
Hom.:
49
AF XY:
0.00551
AC XY:
746
AN XY:
135482
show subpopulations
Gnomad AFR exome
AF:
0.000924
Gnomad AMR exome
AF:
0.0444
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00430
Gnomad SAS exome
AF:
0.000850
Gnomad FIN exome
AF:
0.00412
Gnomad NFE exome
AF:
0.000309
Gnomad OTH exome
AF:
0.00508
GnomAD4 exome
AF:
0.00177
AC:
2591
AN:
1460266
Hom.:
57
Cov.:
32
AF XY:
0.00153
AC XY:
1111
AN XY:
726538
show subpopulations
Gnomad4 AFR exome
AF:
0.000449
Gnomad4 AMR exome
AF:
0.0406
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00671
Gnomad4 SAS exome
AF:
0.000812
Gnomad4 FIN exome
AF:
0.00328
Gnomad4 NFE exome
AF:
0.000129
Gnomad4 OTH exome
AF:
0.00179
GnomAD4 genome
AF:
0.00262
AC:
399
AN:
152152
Hom.:
9
Cov.:
32
AF XY:
0.00285
AC XY:
212
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00135
Gnomad4 AMR
AF:
0.0163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00444
Gnomad4 SAS
AF:
0.000622
Gnomad4 FIN
AF:
0.00397
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000954
Hom.:
1
Bravo
AF:
0.00447
ESP6500AA
AF:
0.00182
AC:
8
ESP6500EA
AF:
0.000581
AC:
5
ExAC
AF:
0.00595
AC:
722
Asia WGS
AF:
0.00462
AC:
16
AN:
3474
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Benign:3
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
Benign, criteria provided, single submitterclinical testingGenomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of PhiladelphiaFeb 13, 2015- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.19
T;.;T;.
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.82
.;.;T;T
MetaRNN
Benign
0.0066
T;T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.2
L;.;L;.
MutationTaster
Benign
0.98
D;D;D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.84
N;.;N;N
REVEL
Benign
0.093
Sift
Benign
0.24
T;.;T;T
Sift4G
Benign
0.16
T;T;T;T
Polyphen
0.12
B;.;B;.
Vest4
0.41
MVP
0.62
MPC
0.71
ClinPred
0.013
T
GERP RS
2.8
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.7
Varity_R
0.089
gMVP
0.50

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.

Other links and lift over

dbSNP: rs79480470; hg19: chr7-112102071; COSMIC: COSV50044891; COSMIC: COSV50044891; API