dbSNP rs17159640: IFRD1:c.-181-4230A>T (chr7-112446278-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000005558.8(IFRD1):c.-181-4230A>T variant causes a intron change. The variant allele was found at a frequency of 0.0632 in 221,618 control chromosomes in the GnomAD database, including 625 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 0.062 ( 386 hom., cov: 33)

Exomes 𝑓: 0.065 ( 239 hom. )

Consequence

IFRD1
ENST00000005558.8 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.01

Publications

7 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:

ENSG00000180019 (HGNC:):

ENSG00000180019 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=-0.54).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFRD1	NM_001007245.3 link	c.-181-4230A>T		intron_variant	Intron 1 of 12		NP_001007246.1	O00458-1A4D0U1
IFRD1	NM_001197080.2 link	c.-56-9485A>T		intron_variant	Intron 1 of 11		NP_001184009.1	O00458-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
IFRD1	ENST00000005558.8 link	c.-181-4230A>T	intron_variant	Intron 1 of 12	1	ENSP00000005558.4	O00458-1
ENSG00000180019	ENST00000321498.5 link	n.98T>A	non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000293153	ENST00000676289.1 link	n.98T>A	non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0622

AC:

9465

AN:

152190

Hom.:

385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0636

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.0744

Gnomad EAS

AF:

0.0728

Gnomad SAS

AF:

0.142

Gnomad FIN

AF:

0.0246

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0449

Gnomad OTH

AF:

0.0737

GnomAD4 exome

AF:

0.0655

AC:

4539

AN:

69310

Hom.:

239

Cov.:

AF XY:

0.0628

AC XY:

2574

AN XY:

40990

show subpopulations

African (AFR)

AF:

0.0658

AC:

115

AN:

1748

American (AMR)

AF:

0.174

AC:

1507

AN:

8662

Ashkenazi Jewish (ASJ)

AF:

0.0671

AC:

AN:

1088

East Asian (EAS)

AF:

0.0800

AC:

304

AN:

3800

South Asian (SAS)

AF:

0.105

AC:

975

AN:

9328

European-Finnish (FIN)

AF:

0.0192

AC:

110

AN:

5730

Middle Eastern (MID)

AF:

0.0593

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.0369

AC:

1333

AN:

36100

Other (OTH)

AF:

0.0420

AC:

115

AN:

2736

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

152

304

456

608

760

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0622

AC:

9478

AN:

152308

Hom.:

386

Cov.:

AF XY:

0.0646

AC XY:

4812

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0637

AC:

2646

AN:

41568

American (AMR)

AF:

0.130

AC:

1983

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0744

AC:

258

AN:

3468

East Asian (EAS)

AF:

0.0722

AC:

374

AN:

5182

South Asian (SAS)

AF:

0.142

AC:

683

AN:

4822

European-Finnish (FIN)

AF:

0.0246

AC:

261

AN:

10618

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0450

AC:

3059

AN:

68042

Other (OTH)

AF:

0.0772

AC:

163

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

453

906

1359

1812

2265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0499

Hom.:

Bravo

AF:

0.0693

Asia WGS

AF:

0.138

AC:

478

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.8

(source)

DANN

Benign

0.67

PhyloP100

7.0

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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