rs6956741

Variant names:

• chr7-112454688-A-G
• rs6956741
• NM_001550.4:c.95-1075A>G

Variant summary

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

The NM_001550.4(IFRD1):​c.95-1075A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 152,114 control chromosomes in the GnomAD database, including 548 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 0.071 (548 hom., cov: 32)
• Consequence: IFRD1 NM_001550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFRD1	NM_001550.4	MANE Select	c.95-1075A>G		intron	N/A	NP_001541.2
	IFRD1	NM_001007245.3		c.95-1075A>G		intron	N/A	NP_001007246.1
	IFRD1	NM_001197079.2		c.-56-1075A>G		intron	N/A	NP_001184008.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFRD1	ENST00000403825.8	TSL:1 MANE Select	c.95-1075A>G		intron	N/A	ENSP00000384477.3
	IFRD1	ENST00000005558.8	TSL:1	c.95-1075A>G		intron	N/A	ENSP00000005558.4
	ENSG00000288640	ENST00000676282.1		n.95-1075A>G		intron	N/A	ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10779 AN: 151996 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0813

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

GnomAD4 genome AF: 0.0709 AC: 10784 AN: 152114 Hom.: 548 Cov.: 32 AF XY: 0.0754 AC XY: 5607 AN XY: 74382

African (AFR) AF: 0.0390 AC: 1617 AN: 41512

American (AMR) AF: 0.135 AC: 2056 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 519 AN: 3472

East Asian (EAS) AF: 0.0723 AC: 374 AN: 5174

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4814

European-Finnish (FIN) AF: 0.0686 AC: 726 AN: 10584

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0618 AC: 4202 AN: 67968

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.0709 Hom.: 979

Bravo AF: 0.0719

Asia WGS AF: 0.185 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.85
PhyloP100		0.49
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: rs6956741; hg19: chr7-112094743;