7-112465699-G-T

Variant names:

• chr7-112465699-G-T
• rs3807213
• NM_001550.4:c.907-2282G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001550.4(IFRD1):​c.907-2282G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,948 control chromosomes in the GnomAD database, including 24,615 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 0.56 (24615 hom., cov: 32)
• Consequence: IFRD1 NM_001550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 26 publications found

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

ENSG00000288640 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001550.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFRD1	NM_001550.4	MANE Select	c.907-2282G>T		intron	N/A	NP_001541.2	O00458-1
	IFRD1	NM_001007245.3		c.907-2282G>T		intron	N/A	NP_001007246.1	O00458-1
	IFRD1	NM_001197079.2		c.757-2282G>T		intron	N/A	NP_001184008.1	O00458-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFRD1	ENST00000403825.8	TSL:1 MANE Select	c.907-2282G>T		intron	N/A	ENSP00000384477.3	O00458-1
	IFRD1	ENST00000005558.8	TSL:1	c.907-2282G>T		intron	N/A	ENSP00000005558.4	O00458-1
	ENSG00000288640	ENST00000676282.1		n.907-2282G>T		intron	N/A	ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85204 AN: 151830 Hom.: 24601 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.561 AC: 85258 AN: 151948 Hom.: 24615 Cov.: 32 AF XY: 0.553 AC XY: 41055 AN XY: 74258

African (AFR) AF: 0.604 AC: 25018 AN: 41430

American (AMR) AF: 0.500 AC: 7633 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2156 AN: 3470

East Asian (EAS) AF: 0.145 AC: 749 AN: 5162

South Asian (SAS) AF: 0.532 AC: 2566 AN: 4820

European-Finnish (FIN) AF: 0.490 AC: 5168 AN: 10544

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40222 AN: 67956

Other (OTH) AF: 0.558 AC: 1175 AN: 2106

Alfa AF: 0.575 Hom.: 44381

Bravo AF: 0.560

Asia WGS AF: 0.387 AC: 1350 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.62
PhyloP100		-0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3807213; hg19: chr7-112105754;