7-112461852-ATTTT-AT

Variant names:

• chr7-112461852-ATTT-A
• rs61603869
• NM_001550.4:c.568-5_568-3delTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001550.4(IFRD1):​c.568-5_568-3delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,036,638 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IFRD1 NM_001550.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000288640 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFRD1	NM_001550.4	c.568-5_568-3delTTT		splice_region_variant, intron_variant	Intron 5 of 11	ENST00000403825.8	NP_001541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFRD1	ENST00000403825.8	c.568-5_568-3delTTT		splice_region_variant, intron_variant	Intron 5 of 11	1	NM_001550.4	ENSP00000384477.3
ENSG00000288640	ENST00000676282.1	n.568-5_568-3delTTT		splice_region_variant, intron_variant	Intron 5 of 14			ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149796 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000137 AC: 21 AN: 153706 Hom.: 1 AF XY: 0.000143 AC XY: 12 AN XY: 83692

Gnomad AFR exome AF: 0.000690

Gnomad AMR exome AF: 0.000227

Gnomad ASJ exome AF: 0.000139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000241

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000459

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000143 AC: 148 AN: 1036638 Hom.: 0 AF XY: 0.000144 AC XY: 76 AN XY: 526854

Gnomad4 AFR exome AF: 0.000338

Gnomad4 AMR exome AF: 0.000189

Gnomad4 ASJ exome AF: 0.0000465

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000144

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000152

Gnomad4 OTH exome AF: 0.000114

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149796 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 73028

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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;