7-112455988-A-G

Variant names:

• chr7-112455988-A-G
• rs11773535
• NM_001550.4:c.200-14A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001550.4(IFRD1):​c.200-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,404,526 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: IFRD1 NM_001550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.456
• Publications: 3 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High AC in GnomAdExome4 at 20 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.200-14A>G		intron	N/A	NP_001541.2	O00458-1
	IFRD1	NM_001007245.3		c.200-14A>G		intron	N/A	NP_001007246.1	O00458-1
	IFRD1	NM_001197079.2		c.50-14A>G		intron	N/A	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.200-14A>G		intron	N/A	ENSP00000384477.3	O00458-1
	IFRD1	ENST00000005558.8	TSL:1	c.200-14A>G		intron	N/A	ENSP00000005558.4	O00458-1
	ENSG00000288640	ENST00000676282.1		n.200-14A>G		intron	N/A	ENSP00000501830.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250050 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000142 AC: 20 AN: 1404526 Hom.: 0 Cov.: 25 AF XY: 0.00000997 AC XY: 7 AN XY: 702396

African (AFR) AF: 0.00 AC: 0 AN: 32408

American (AMR) AF: 0.0000896 AC: 4 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25760

East Asian (EAS) AF: 0.00 AC: 0 AN: 39420

South Asian (SAS) AF: 0.00 AC: 0 AN: 85060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.0000151 AC: 16 AN: 1059834

Other (OTH) AF: 0.00 AC: 0 AN: 58450

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000161 Hom.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.7
DANN	Benign	0.75
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11773535; hg19: chr7-112096043;