NM_001550.4:c.142A>T

Variant names:

• chr7-112455810-A-T
• NM_001550.4:c.142A>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001550.4(IFRD1):​c.142A>T​(p.Ile48Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,274 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IFRD1 NM_001550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.58

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3932237).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFRD1	NM_001550.4	c.142A>T	p.Ile48Phe	missense_variant	Exon 2 of 12	ENST00000403825.8	NP_001541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFRD1	ENST00000403825.8	c.142A>T	p.Ile48Phe	missense_variant	Exon 2 of 12	1	NM_001550.4	ENSP00000384477.3
ENSG00000288640	ENST00000676282.1	n.142A>T		non_coding_transcript_exon_variant	Exon 2 of 15			ENSP00000501830.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461274 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726976

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	T;.;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	.;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.39	T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.1	M;.;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.29	N;D;N;N
REVEL	Benign	0.28
Sift	Benign	0.71	T;D;T;T
Sift4G	Uncertain	0.058	T;D;T;D
Polyphen		1.0	D;.;D;D
Vest4		0.63
MutPred		0.42		Gain of catalytic residue at I48 (P = 0.0297);Gain of catalytic residue at I48 (P = 0.0297);Gain of catalytic residue at I48 (P = 0.0297);Gain of catalytic residue at I48 (P = 0.0297);
MVP		0.46
MPC		1.6
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-112095865;