Variant chr7-112461856-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001550.4(IFRD1):c.568-10T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,395,098 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 10 hom. )

Consequence

IFRD1
NM_001550.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008750

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.525

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 7-112461856-T-A is Benign according to our data. Variant chr7-112461856-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1284633.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-112461856-T-A is described in Lovd as [Benign]. Variant chr7-112461856-T-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFRD1	NM_001550.4 linkuse as main transcript	c.568-10T>A		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.568-10T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001550.4	P3	O00458-1

Frequencies

GnomAD3 genomes

AF:

0.00116

AC:

175

AN:

150928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000763

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00309

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00134

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.000965

GnomAD3 exomes

AF:

0.00241

AC:

527

AN:

218924

Hom.:

AF XY:

0.00184

AC XY:

220

AN XY:

119526

show subpopulations

Gnomad AFR exome

AF:

0.000454

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.000109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000440

Gnomad FIN exome

AF:

0.000929

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00133

AC:

1659

AN:

1244056

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

780

AN XY:

627572

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.00983

Gnomad4 ASJ exome

AF:

0.0000820

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000470

Gnomad4 FIN exome

AF:

0.00115

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00116

AC:

175

AN:

151042

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

73862

show subpopulations

Gnomad4 AFR

AF:

0.000761

Gnomad4 AMR

AF:

0.00309

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00134

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00170

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.66

CADD

Benign

1.2

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00088

dbscSNV1_RF

Benign

0.066

SpliceAI score (max)

0.070

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