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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 18
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

IFRD1 links:

ENSG00000288640 (HGNC:):

ENSG00000288640 links:

Genome browser will be placed here

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 VariationId is 1284633.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 175 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001550.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFRD1	NM_001550.4	MANE Select	c.568-10T>A	intron	N/A	NP_001541.2	O00458-1
IFRD1	NM_001007245.3		c.568-10T>A	intron	N/A	NP_001007246.1	O00458-1
IFRD1	NM_001197079.2		c.418-10T>A	intron	N/A	NP_001184008.1	O00458-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IFRD1	ENST00000403825.8	TSL:1 MANE Select	c.568-10T>A	intron	N/A	ENSP00000384477.3	O00458-1
IFRD1	ENST00000005558.8	TSL:1	c.568-10T>A	intron	N/A	ENSP00000005558.4	O00458-1
ENSG00000288640	ENST00000676282.1		n.568-10T>A	intron	N/A	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

African (AFR)

AF:

0.000867

AC:

AN:

27676

American (AMR)

AF:

0.00983

AC:

412

AN:

41932

Ashkenazi Jewish (ASJ)

AF:

0.0000820

AC:

AN:

24392

East Asian (EAS)

AF:

0.00

AC:

AN:

38116

South Asian (SAS)

AF:

0.000470

AC:

AN:

78768

European-Finnish (FIN)

AF:

0.00115

AC:

AN:

51308

Middle Eastern (MID)

AF:

0.00132

AC:

AN:

3782

European-Non Finnish (NFE)

AF:

0.00114

AC:

1058

AN:

925500

Other (OTH)

AF:

0.00118

AC:

AN:

52582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

123

184

246

307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

African (AFR)

AF:

0.000761

AC:

AN:

40724

American (AMR)

AF:

0.00309

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000623

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00134

AC:

AN:

10446

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00115

AC:

AN:

67882

Other (OTH)

AF:

0.000955

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.2

(source)

DANN

Benign

0.84

PhyloP100

0.53

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over