chr7-112458965-A-G

Variant names:

• chr7-112458965-A-G
• rs150651401
• NM_001550.4:c.514A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001550.4(IFRD1):​c.514A>G​(p.Ile172Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000408 in 1,613,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: IFRD1 NM_001550.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:2
• Conservation: PhyloP100: 0.281
• 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]

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0070363283).
• BP6: Variant 7-112458965-A-G is Benign according to our data. Variant chr7-112458965-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 637690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 183 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFRD1	NM_001550.4	MANE Select	c.514A>G	p.Ile172Val	missense	Exon 5 of 12	NP_001541.2	O00458-1
	IFRD1	NM_001007245.3		c.514A>G	p.Ile172Val	missense	Exon 6 of 13	NP_001007246.1	O00458-1
	IFRD1	NM_001197079.2		c.364A>G	p.Ile122Val	missense	Exon 5 of 12	NP_001184008.1	O00458-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFRD1	ENST00000403825.8	TSL:1 MANE Select	c.514A>G	p.Ile172Val	missense	Exon 5 of 12	ENSP00000384477.3	O00458-1
	IFRD1	ENST00000005558.8	TSL:1	c.514A>G	p.Ile172Val	missense	Exon 6 of 13	ENSP00000005558.4	O00458-1
	ENSG00000288640	ENST00000676282.1		n.514A>G		non_coding_transcript_exon	Exon 5 of 15	ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.00120 AC: 182 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000437 AC: 110 AN: 251434 AF XY: 0.000309

Gnomad AFR exome AF: 0.00320

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000281

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000326 AC: 476 AN: 1461664 Hom.: 0 Cov.: 31 AF XY: 0.000297 AC XY: 216 AN XY: 727150

African (AFR) AF: 0.00269 AC: 90 AN: 33470

American (AMR) AF: 0.000604 AC: 27 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.000289 AC: 321 AN: 1111828

Other (OTH) AF: 0.000447 AC: 27 AN: 60386

GnomAD4 genome AF: 0.00120 AC: 183 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.00114 AC XY: 85 AN XY: 74440

African (AFR) AF: 0.00315 AC: 131 AN: 41544

American (AMR) AF: 0.00216 AC: 33 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68014

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000534 Hom.: 0

Bravo AF: 0.00122

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000478 AC: 58

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Charcot-Marie-Tooth disease (1)
-	-	1	IFRD1-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.042
DANN	Benign	0.47
DEOGEN2	Benign	0.080	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.21	N
PhyloP100		0.28
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.061
Sift	Benign	0.75	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.20
MVP		0.25
MPC		0.37
ClinPred		0.0015	T
GERP RS		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.017
gMVP		0.11
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs150651401; hg19: chr7-112099020;