rs4730550

Variant names:

• chr7-112469668-G-T
• rs4730550
• NM_001550.4:c.1041+1553G>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.1041+1553G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 152,096 control chromosomes in the GnomAD database, including 307 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 0.061 (307 hom., cov: 31)
• Consequence: IFRD1 NM_001550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFRD1	NM_001550.4	c.1041+1553G>T		intron_variant	Intron 9 of 11	ENST00000403825.8	NP_001541.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFRD1	ENST00000403825.8	c.1041+1553G>T		intron_variant	Intron 9 of 11	1	NM_001550.4	ENSP00000384477.3
ENSG00000288640	ENST00000676282.1	n.1041+1553G>T		intron_variant	Intron 9 of 14			ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9260 AN: 151978 Hom.: 306 Cov.: 31

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.0956

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0544

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

GnomAD4 genome AF: 0.0609 AC: 9265 AN: 152096 Hom.: 307 Cov.: 31 AF XY: 0.0595 AC XY: 4422 AN XY: 74342

African (AFR) AF: 0.0513 AC: 2130 AN: 41484

American (AMR) AF: 0.0414 AC: 632 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3468

East Asian (EAS) AF: 0.0709 AC: 367 AN: 5178

South Asian (SAS) AF: 0.0956 AC: 460 AN: 4810

European-Finnish (FIN) AF: 0.0335 AC: 354 AN: 10576

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4872 AN: 67988

Other (OTH) AF: 0.0539 AC: 114 AN: 2116

Alfa AF: 0.0683 Hom.: 608

Bravo AF: 0.0603

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.75
PhyloP100		-0.84
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: rs4730550; hg19: chr7-112109723;