Variant 7-112456015-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001550.4(IFRD1):c.213T>A(p.Leu71=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00979 in 1,603,320 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 7 hom., cov: 33)

Exomes 𝑓: 0.010 ( 95 hom. )

Consequence

IFRD1
NM_001550.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.128

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 7-112456015-T-A is Benign according to our data. Variant chr7-112456015-T-A is described in ClinVar as [Benign]. Clinvar id is 774663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-112456015-T-A is described in Lovd as [Benign]. Variant chr7-112456015-T-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.128 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFRD1	NM_001550.4 linkuse as main transcript	c.213T>A	p.Leu71=	synonymous_variant	3/12	ENST00000403825.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFRD1	ENST00000403825.8 linkuse as main transcript	c.213T>A	p.Leu71=	synonymous_variant	3/12	1	NM_001550.4	P3	O00458-1

Frequencies

GnomAD3 genomes

AF:

0.00758

AC:

1153

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0177

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0105

Gnomad OTH

AF:

0.00768

GnomAD3 exomes

AF:

0.00798

AC:

2005

AN:

251246

Hom.:

AF XY:

0.00794

AC XY:

1078

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00367

Gnomad ASJ exome

AF:

0.00734

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00464

Gnomad FIN exome

AF:

0.0184

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.00898

GnomAD4 exome

AF:

0.0100

AC:

14546

AN:

1451036

Hom.:

Cov.:

AF XY:

0.00971

AC XY:

7019

AN XY:

722764

show subpopulations

Gnomad4 AFR exome

AF:

0.00186

Gnomad4 AMR exome

AF:

0.00463

Gnomad4 ASJ exome

AF:

0.00617

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00465

Gnomad4 FIN exome

AF:

0.0167

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.00871

GnomAD4 genome

AF:

0.00756

AC:

1151

AN:

152284

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

586

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00195

Gnomad4 AMR

AF:

0.00700

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.0177

Gnomad4 NFE

AF:

0.0105

Gnomad4 OTH

AF:

0.00760

Alfa

AF:

0.00958

Hom.:

Bravo

AF:

0.00707

Asia WGS

AF:

0.00260

AC:

AN:

3476

EpiCase

AF:

0.00943

EpiControl

AF:

0.00943

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	IFRD1: BP4, BP7, BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.9

DANN

Benign

0.72

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

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