Genetic Variant IFRD1:n.1138C>T (chr7-112475603-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000489994.5(IFRD1):n.1138C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 809,472 control chromosomes in the GnomAD database, including 93,673 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 16792 hom., cov: 32)

Exomes 𝑓: 0.47 ( 76881 hom. )

Consequence

IFRD1
ENST00000489994.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.189

Publications

27 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFRD1	NM_001550.4 link	c.*84C>T		3_prime_UTR_variant	Exon 12 of 12	ENST00000403825.8	NP_001541.2	O00458-1A4D0U1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000288640	ENST00000676282.1 link	n.*84C>T	non_coding_transcript_exon_variant	Exon 12 of 15			ENSP00000501830.1
IFRD1	ENST00000403825.8 link	c.*84C>T	3_prime_UTR_variant	Exon 12 of 12	1	NM_001550.4	ENSP00000384477.3	O00458-1
ENSG00000288640	ENST00000676282.1 link	n.*84C>T	3_prime_UTR_variant	Exon 12 of 15			ENSP00000501830.1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70442

AN:

151672

Hom.:

16790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.433

Gnomad AMI

AF:

0.448

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.533

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.426

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.515

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.474

AC:

311507

AN:

657682

Hom.:

76881

Cov.:

AF XY:

0.474

AC XY:

165774

AN XY:

349942

show subpopulations

African (AFR)

AF:

0.425

AC:

7179

AN:

16906

American (AMR)

AF:

0.391

AC:

12879

AN:

32964

Ashkenazi Jewish (ASJ)

AF:

0.517

AC:

10596

AN:

20492

East Asian (EAS)

AF:

0.122

AC:

3963

AN:

32358

South Asian (SAS)

AF:

0.430

AC:

26451

AN:

61462

European-Finnish (FIN)

AF:

0.469

AC:

16694

AN:

35584

Middle Eastern (MID)

AF:

0.423

AC:

1226

AN:

2896

European-Non Finnish (NFE)

AF:

0.514

AC:

216682

AN:

421568

Other (OTH)

AF:

0.473

AC:

15837

AN:

33452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

8058

16116

24173

32231

40289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2792

5584

8376

11168

13960

<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:

0.464

AC:

70468

AN:

151790

Hom.:

16792

Cov.:

AF XY:

0.459

AC XY:

34062

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.432

AC:

17884

AN:

41362

American (AMR)

AF:

0.437

AC:

6674

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.533

AC:

1847

AN:

3468

East Asian (EAS)

AF:

0.145

AC:

747

AN:

5160

South Asian (SAS)

AF:

0.426

AC:

2049

AN:

4812

European-Finnish (FIN)

AF:

0.456

AC:

4791

AN:

10506

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.515

AC:

34956

AN:

67900

Other (OTH)

AF:

0.471

AC:

992

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1881

3762

5642

7523

9404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.481

Hom.:

19662

Bravo

AF:

0.459

Asia WGS

AF:

0.339

AC:

1179

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

(source)

DANN

Benign

0.58

PhyloP100

-0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over