chr7-112461856-T-G

Variant names:

• chr7-112461856-T-G
• rs565300368
• NM_001550.4:c.568-10T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001550.4(IFRD1):​c.568-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000803 in 1,245,470 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: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: IFRD1 NM_001550.4 intron
• Scores: Splicing: ADA: 0.0007484
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.525
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

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.568-10T>G		intron	N/A	NP_001541.2	O00458-1
	IFRD1	NM_001007245.3		c.568-10T>G		intron	N/A	NP_001007246.1	O00458-1
	IFRD1	NM_001197079.2		c.418-10T>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.568-10T>G		intron	N/A	ENSP00000384477.3	O00458-1
	IFRD1	ENST00000005558.8	TSL:1	c.568-10T>G		intron	N/A	ENSP00000005558.4	O00458-1
	ENSG00000288640	ENST00000676282.1		n.568-10T>G		intron	N/A	ENSP00000501830.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.03e-7 AC: 1 AN: 1245470 Hom.: 0 Cov.: 20 AF XY: 0.00000159 AC XY: 1 AN XY: 628242

African (AFR) AF: 0.00 AC: 0 AN: 27702

American (AMR) AF: 0.00 AC: 0 AN: 41960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24402

East Asian (EAS) AF: 0.00 AC: 0 AN: 38116

South Asian (SAS) AF: 0.0000127 AC: 1 AN: 78790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3786

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 926754

Other (OTH) AF: 0.00 AC: 0 AN: 52634

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	2.4
DANN	Benign	0.81
PhyloP100		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00075
dbscSNV1_RF	Benign	0.066
SpliceAI score (max)		0.050		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: rs565300368; hg19: chr7-112101911;