7-112462016-C-G

Variant names:

Variant summary

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

The NM_001550.4(IFRD1):c.634C>G(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 (★★).

Frequency

Genomes: 𝑓 0.0026 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 57 hom. )

Consequence

IFRD1
NM_001550.4 missense

Scores

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]

IFRD1 links:

ENSG00000288640 (HGNC:):

ENSG00000288640 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=0.0065864623).

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 rank	MANE	Protein	UniProt
IFRD1	NM_001550.4 link	c.634C>G	p.Leu212Val	missense_variant	Exon 7 of 12	ENST00000403825.8	NP_001541.2	O00458-1A4D0U1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFRD1	ENST00000403825.8 link	c.634C>G	p.Leu212Val	missense_variant	Exon 7 of 12	1	NM_001550.4	ENSP00000384477.3		O00458-1
ENSG00000288640	ENST00000676282.1 link	n.634C>G		non_coding_transcript_exon_variant	Exon 7 of 15			ENSP00000501830.1

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

392

AN:

152034

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00447

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00595

AC:

722

Asia WGS

AF:

0.00462

AC:

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

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 13, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;.;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.82

.;.;T;T

MetaRNN

Benign

0.0066

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

L;.;L;.

PrimateAI

Benign

0.38

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

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.

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