Genetic Variant IFRD1:c.568-10T>A (chr7-112461856-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001550.4(IFRD1):c.568-10T>A variant causes a 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 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:

ENSG00000288640 (HGNC:):

ENSG00000288640 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IFRD1	NM_001550.4 link	c.568-10T>A		intron_variant	Intron 5 of 11	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.568-10T>A		intron_variant	Intron 5 of 11	1	NM_001550.4	ENSP00000384477.3		O00458-1
ENSG00000288640	ENST00000676282.1 link	n.568-10T>A		intron_variant	Intron 5 of 14			ENSP00000501830.1

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

GnomAD2 exomes

AF:

0.00241

AC:

527

AN:

218924

AF XY:

0.00184

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 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

AC:

AN:

27676

Gnomad4 AMR exome

AF:

0.00983

AC:

412

AN:

41932

Gnomad4 ASJ exome

AF:

0.0000820

AC:

AN:

24392

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

38116

Gnomad4 SAS exome

AF:

0.000470

AC:

AN:

78768

Gnomad4 FIN exome

AF:

0.00115

AC:

AN:

51308

Gnomad4 NFE exome

AF:

0.00114

AC:

1058

AN:

925500

Gnomad4 Remaining exome

AF:

0.00118

AC:

AN:

52582

Heterozygous variant carriers

123

184

246

307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

AC:

0.000761222

AN:

0.000761222

Gnomad4 AMR

AF:

0.00309

AC:

0.00308764

AN:

0.00308764

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000623

AC:

0.000622665

AN:

0.000622665

Gnomad4 FIN

AF:

0.00134

AC:

0.00134023

AN:

0.00134023

Gnomad4 NFE

AF:

0.00115

AC:

0.00114905

AN:

0.00114905

Gnomad4 OTH

AF:

0.000955

AC:

0.00095511

AN:

0.00095511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.2

DANN

Benign

0.84

Mutation Taster

=100/0

polymorphism

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