chr7-112450740-G-A

Variant names:

• chr7-112450740-G-A
• rs767342314
• NM_001550.4:c.52G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001550.4(IFRD1):​c.52G>A​(p.Gly18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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)
• Consequence: IFRD1 NM_001550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.73

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093826205).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFRD1	NM_001550.4	c.52G>A	p.Gly18Ser	missense_variant	Exon 1 of 12	ENST00000403825.8	NP_001541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFRD1	ENST00000403825.8	c.52G>A	p.Gly18Ser	missense_variant	Exon 1 of 12	1	NM_001550.4	ENSP00000384477.3
ENSG00000288640	ENST00000676282.1	n.52G>A		non_coding_transcript_exon_variant	Exon 1 of 15			ENSP00000501830.1
ENSG00000288634	ENST00000675268.1	c.*95G>A		downstream_gene_variant				ENSP00000501715.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000411 AC: 1 AN: 243364 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 133466

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000918

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.00000836 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;T;.;T;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.63	T;.;T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.094	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;N;.;N;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-6.0	D;N;N;N;N
REVEL	Benign	0.090
Sift	Benign	0.14	.;T;T;T;T
Sift4G	Pathogenic	0.0	D;T;T;T;T
Polyphen		0.0020, 0.0030	.;B;.;B;B
Vest4		0.38, 0.38, 0.36
MutPred		0.17		Gain of glycosylation at G18 (P = 5e-04);Gain of glycosylation at G18 (P = 5e-04);Gain of glycosylation at G18 (P = 5e-04);Gain of glycosylation at G18 (P = 5e-04);Gain of glycosylation at G18 (P = 5e-04);
MVP		0.38
MPC		0.44
ClinPred		0.40	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.094
gMVP		0.22

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

Other links and lift over

dbSNP: rs767342314; hg19: chr7-112090795;