7-112457066-C-T

Variant names:

• chr7-112457066-C-T
• rs6968084
• NM_001550.4:c.409+28C>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.409+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,606,626 control chromosomes in the GnomAD database, including 20,669 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 0.16 (2197 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18472 hom.)
• Consequence: IFRD1 NM_001550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 20 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 (MetaRNN=0.0034398139).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.292 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.409+28C>T		intron	N/A	NP_001541.2
	IFRD1	NM_001007245.3		c.409+28C>T		intron	N/A	NP_001007246.1
	IFRD1	NM_001197079.2		c.259+28C>T		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.409+28C>T		intron	N/A	ENSP00000384477.3
	IFRD1	ENST00000005558.8	TSL:1	c.409+28C>T		intron	N/A	ENSP00000005558.4
	ENSG00000288640	ENST00000676282.1		n.409+28C>T		intron	N/A	ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24860 AN: 151952 Hom.: 2195 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.174 AC: 43694 AN: 250674 AF XY: 0.178

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.223

Gnomad ASJ exome AF: 0.230

Gnomad EAS exome AF: 0.144

Gnomad FIN exome AF: 0.102

Gnomad NFE exome AF: 0.135

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.151 AC: 219220 AN: 1454558 Hom.: 18472 Cov.: 30 AF XY: 0.155 AC XY: 112396 AN XY: 724086

African (AFR) AF: 0.196 AC: 6526 AN: 33302

American (AMR) AF: 0.215 AC: 9616 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 6023 AN: 26058

East Asian (EAS) AF: 0.126 AC: 5005 AN: 39596

South Asian (SAS) AF: 0.297 AC: 25545 AN: 86076

European-Finnish (FIN) AF: 0.102 AC: 5387 AN: 52866

Middle Eastern (MID) AF: 0.172 AC: 991 AN: 5746

European-Non Finnish (NFE) AF: 0.135 AC: 149860 AN: 1106098

Other (OTH) AF: 0.171 AC: 10267 AN: 60128

GnomAD4 genome AF: 0.164 AC: 24881 AN: 152068 Hom.: 2197 Cov.: 32 AF XY: 0.166 AC XY: 12302 AN XY: 74330

African (AFR) AF: 0.198 AC: 8224 AN: 41474

American (AMR) AF: 0.192 AC: 2932 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3470

East Asian (EAS) AF: 0.143 AC: 739 AN: 5176

South Asian (SAS) AF: 0.305 AC: 1471 AN: 4824

European-Finnish (FIN) AF: 0.103 AC: 1086 AN: 10560

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9112 AN: 67968

Other (OTH) AF: 0.168 AC: 354 AN: 2110

Alfa AF: 0.150 Hom.: 6321

Bravo AF: 0.169

TwinsUK AF: 0.130 AC: 483

ALSPAC AF: 0.137 AC: 529

ESP6500AA AF: 0.201 AC: 886

ESP6500EA AF: 0.138 AC: 1189

ExAC AF: 0.176 AC: 21364

Asia WGS AF: 0.268 AC: 930 AN: 3478

EpiCase AF: 0.140

EpiControl AF: 0.143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	9.1
DANN	Benign	0.53
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.011
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.0010
Sift	Pathogenic	0.0	D
Polyphen		0.058	B
Vest4		0.044
ClinPred		0.014	T
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs6968084; hg19: chr7-112097121; COSMIC: COSV50043832; COSMIC: COSV50043832;