7-112461852-ATT-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001550.4(IFRD1):c.568-4_568-3del 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 0.0846 in 1,156,466 control chromosomes in the GnomAD database, including 6,856 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.071 (538 hom., cov: 27)
  • Exomes 𝑓: 0.087 (6318 hom.)
• Consequence: IFRD1 NM_001550.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.424

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 7-112461852-ATT-A is Benign according to our data. Variant chr7-112461852-ATT-A is described in ClinVar as [Benign]. Clinvar id is 1284576.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-112461852-ATT-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFRD1	NM_001550.4	c.568-4_568-3del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000403825.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFRD1	ENST00000403825.8	c.568-4_568-3del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001550.4	P3

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10690 AN: 149698 Hom.: 536 Cov.: 27

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0780

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0620

Gnomad OTH AF: 0.0810

GnomAD3 exomes AF: 0.146 AC: 22411 AN: 153706 Hom.: 2238 AF XY: 0.149 AC XY: 12474 AN XY: 83692

Gnomad AFR exome AF: 0.0535

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.117

Gnomad SAS exome AF: 0.263

Gnomad FIN exome AF: 0.0899

Gnomad NFE exome AF: 0.0943

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.0866 AC: 87161 AN: 1006670 Hom.: 6318 AF XY: 0.0915 AC XY: 46810 AN XY: 511748

Gnomad4 AFR exome AF: 0.0420

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.0924

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.0810

Gnomad4 NFE exome AF: 0.0668

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.0714 AC: 10695 AN: 149796 Hom.: 538 Cov.: 27 AF XY: 0.0759 AC XY: 5547 AN XY: 73068

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0779

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0716

Gnomad4 NFE AF: 0.0620

Gnomad4 OTH AF: 0.0861

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:2

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	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs61603869; hg19: chr7-112101907;