Variant chr7-112461996-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001550.4(IFRD1):c.619-5A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,609,074 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 29 hom. )

Consequence

IFRD1
NM_001550.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002821

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.10

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 7-112461996-A-G is Benign according to our data. Variant chr7-112461996-A-G is described in ClinVar as [Benign]. Clinvar id is 713158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-112461996-A-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFRD1	NM_001550.4 linkuse as main transcript	c.619-5A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000403825.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFRD1	ENST00000403825.8 linkuse as main transcript	c.619-5A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001550.4	P3	O00458-1

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

233

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0101

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00268

AC:

672

AN:

250596

Hom.:

AF XY:

0.00334

AC XY:

452

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00203

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00232

AC:

3381

AN:

1456870

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

1957

AN XY:

725162

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000806

Gnomad4 ASJ exome

AF:

0.00441

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.000469

Gnomad4 NFE exome

AF:

0.00179

Gnomad4 OTH exome

AF:

0.00267

GnomAD4 genome

AF:

0.00154

AC:

235

AN:

152204

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00173

Hom.:

Bravo

AF:

0.00122

Asia WGS

AF:

0.00144

AC:

AN:

3476

EpiCase

AF:

0.00218

EpiControl

AF:

0.00314

ClinVar

Significance: Benign

Submissions summary: Benign:4

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, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.7

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00028

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.050

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