NM_001550.4:c.213T>A

Variant names:

• chr7-112456015-T-A
• rs117086064
• NM_001550.4:c.213T>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001550.4(IFRD1):​c.213T>A​(p.Leu71Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00979 in 1,603,320 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (7 hom., cov: 33)
  • Exomes 𝑓: 0.010 (95 hom.)
• Consequence: IFRD1 NM_001550.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.128
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-112456015-T-A is Benign according to our data. Variant chr7-112456015-T-A is described in ClinVar as Benign. ClinVar VariationId is 774663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.128 with no splicing effect.
• BS2: High AC in GnomAd4 at 1151 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.213T>A	p.Leu71Leu	synonymous	Exon 3 of 12	NP_001541.2	O00458-1
	IFRD1	NM_001007245.3		c.213T>A	p.Leu71Leu	synonymous	Exon 4 of 13	NP_001007246.1	O00458-1
	IFRD1	NM_001197079.2		c.63T>A	p.Leu21Leu	synonymous	Exon 3 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.213T>A	p.Leu71Leu	synonymous	Exon 3 of 12	ENSP00000384477.3	O00458-1
	IFRD1	ENST00000005558.8	TSL:1	c.213T>A	p.Leu71Leu	synonymous	Exon 4 of 13	ENSP00000005558.4	O00458-1
	ENSG00000288640	ENST00000676282.1		n.213T>A		non_coding_transcript_exon	Exon 3 of 15	ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.00758 AC: 1153 AN: 152166 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00700

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00768

GnomAD2 exomes AF: 0.00798 AC: 2005 AN: 251246 AF XY: 0.00794

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00367

Gnomad ASJ exome AF: 0.00734

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0184

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00898

GnomAD4 exome AF: 0.0100 AC: 14546 AN: 1451036 Hom.: 95 Cov.: 28 AF XY: 0.00971 AC XY: 7019 AN XY: 722764

African (AFR) AF: 0.00186 AC: 62 AN: 33254

American (AMR) AF: 0.00463 AC: 207 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00617 AC: 161 AN: 26076

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39594

South Asian (SAS) AF: 0.00465 AC: 400 AN: 86022

European-Finnish (FIN) AF: 0.0167 AC: 889 AN: 53366

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5752

European-Non Finnish (NFE) AF: 0.0112 AC: 12296 AN: 1102220

Other (OTH) AF: 0.00871 AC: 523 AN: 60042

GnomAD4 genome AF: 0.00756 AC: 1151 AN: 152284 Hom.: 7 Cov.: 33 AF XY: 0.00787 AC XY: 586 AN XY: 74472

African (AFR) AF: 0.00195 AC: 81 AN: 41554

American (AMR) AF: 0.00700 AC: 107 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00455 AC: 22 AN: 4832

European-Finnish (FIN) AF: 0.0177 AC: 188 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0105 AC: 711 AN: 68022

Other (OTH) AF: 0.00760 AC: 16 AN: 2106

Alfa AF: 0.00958 Hom.: 3

Bravo AF: 0.00707

Asia WGS AF: 0.00260 AC: 9 AN: 3476

EpiCase AF: 0.00943

EpiControl AF: 0.00943

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.9
DANN	Benign	0.72
PhyloP100		-0.13
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=97/3	polymorphism

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: rs117086064; hg19: chr7-112096070;