Variant 7-112455988-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001550.4(IFRD1):c.200-14A>C 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 0.0267 in 1,556,428 control chromosomes in the GnomAD database, including 668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.022 ( 59 hom., cov: 33)

Exomes 𝑓: 0.027 ( 609 hom. )

Consequence

IFRD1
NM_001550.4 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign no assertion criteria provided B:3

Conservation

PhyloP100: -0.456

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 7-112455988-A-C is Benign according to our data. Variant chr7-112455988-A-C is described in ClinVar as [Benign]. Clinvar id is 1284865.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-112455988-A-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (3382/152202) while in subpopulation NFE AF= 0.0342 (2323/68000). AF 95% confidence interval is 0.033. There are 59 homozygotes in gnomad4. There are 1584 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFRD1	NM_001550.4 linkuse as main transcript	c.200-14A>C		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.200-14A>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001550.4	P3	O00458-1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3384

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00563

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0203

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0213

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0342

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0214

AC:

5362

AN:

250050

Hom.:

AF XY:

0.0219

AC XY:

2961

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.00562

Gnomad AMR exome

AF:

0.0141

Gnomad ASJ exome

AF:

0.0350

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00350

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0331

Gnomad OTH exome

AF:

0.0254

GnomAD4 exome

AF:

0.0271

AC:

38109

AN:

1404226

Hom.:

609

Cov.:

AF XY:

0.0266

AC XY:

18700

AN XY:

702260

show subpopulations

Gnomad4 AFR exome

AF:

0.00518

Gnomad4 AMR exome

AF:

0.0153

Gnomad4 ASJ exome

AF:

0.0341

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00459

Gnomad4 FIN exome

AF:

0.0195

Gnomad4 NFE exome

AF:

0.0314

Gnomad4 OTH exome

AF:

0.0257

GnomAD4 genome

AF:

0.0222

AC:

3382

AN:

152202

Hom.:

Cov.:

AF XY:

0.0213

AC XY:

1584

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00561

Gnomad4 AMR

AF:

0.0203

Gnomad4 ASJ

AF:

0.0378

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0213

Gnomad4 NFE

AF:

0.0342

Gnomad4 OTH

AF:

0.0242

Alfa

AF:

0.0249

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.4

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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