ENST00000005558.8:c.-182+4614G>C

Variant names:

• chr7-112428046-G-C
• rs728273
• ENST00000005558.8:c.-182+4614G>C

Variant summary

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

The ENST00000005558.8(IFRD1):​c.-182+4614G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,968 control chromosomes in the GnomAD database, including 21,363 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 0.51 (21363 hom., cov: 32)
• Consequence: IFRD1 ENST00000005558.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 6 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]

LOC105375457 (HGNC:):

ZNF277-AS1 (HGNC:55828): (ZNF277 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000005558.8. 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_001007245.3		c.-182+4614G>C		intron	N/A	NP_001007246.1	O00458-1
	IFRD1	NM_001197080.2		c.-57+4614G>C		intron	N/A	NP_001184009.1	O00458-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFRD1	ENST00000005558.8	TSL:1	c.-182+4614G>C		intron	N/A	ENSP00000005558.4	O00458-1
	IFRD1	ENST00000675578.1		c.-112+4614G>C		intron	N/A	ENSP00000502336.1	O00458-1
	IFRD1	ENST00000621379.4	TSL:2	c.-57+4614G>C		intron	N/A	ENSP00000483255.1	O00458-2

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77947 AN: 151848 Hom.: 21360 Cov.: 32

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.353

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.513 AC: 77961 AN: 151968 Hom.: 21363 Cov.: 32 AF XY: 0.515 AC XY: 38286 AN XY: 74290

African (AFR) AF: 0.320 AC: 13279 AN: 41436

American (AMR) AF: 0.508 AC: 7759 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1792 AN: 3472

East Asian (EAS) AF: 0.638 AC: 3291 AN: 5162

South Asian (SAS) AF: 0.436 AC: 2100 AN: 4822

European-Finnish (FIN) AF: 0.679 AC: 7178 AN: 10576

Middle Eastern (MID) AF: 0.341 AC: 99 AN: 290

European-Non Finnish (NFE) AF: 0.603 AC: 40974 AN: 67934

Other (OTH) AF: 0.497 AC: 1044 AN: 2102

Alfa AF: 0.575 Hom.: 3242

Bravo AF: 0.492

Asia WGS AF: 0.473 AC: 1641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.84
DANN	Benign	0.37
PhyloP100		-0.29
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs728273;

hg19: chr7-112068101;