NM_001550.4:c.200-14A>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001550.4(IFRD1):​c.200-14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 1,556,428 control chromosomes in the GnomAD database, including 668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (59 hom., cov: 33)
  • Exomes 𝑓: 0.027 (609 hom.)
• Consequence: IFRD1 NM_001550.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:4
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-112455988-A-C is Benign according to our data. Variant chr7-112455988-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1284865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0222 (3382/152202) while in subpopulation NFE AF = 0.0342 (2323/68000). AF 95% confidence interval is 0.033. There are 59 homozygotes in GnomAd4. There are 1584 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3382 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>C		intron	N/A	NP_001541.2	O00458-1
	IFRD1	NM_001007245.3		c.200-14A>C		intron	N/A	NP_001007246.1	O00458-1
	IFRD1	NM_001197079.2		c.50-14A>C		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>C		intron	N/A	ENSP00000384477.3	O00458-1
	IFRD1	ENST00000005558.8	TSL:1	c.200-14A>C		intron	N/A	ENSP00000005558.4	O00458-1
	ENSG00000288640	ENST00000676282.1		n.200-14A>C		intron	N/A	ENSP00000501830.1

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3384 AN: 152084 Hom.: 59 Cov.: 33

Gnomad AFR AF: 0.00563

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0213

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0214 AC: 5362 AN: 250050 AF XY: 0.0219

Gnomad AFR exome AF: 0.00562

Gnomad AMR exome AF: 0.0141

Gnomad ASJ exome AF: 0.0350

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0198

Gnomad NFE exome AF: 0.0331

Gnomad OTH exome AF: 0.0254

GnomAD4 exome AF: 0.0271 AC: 38109 AN: 1404226 Hom.: 609 Cov.: 25 AF XY: 0.0266 AC XY: 18700 AN XY: 702260

African (AFR) AF: 0.00518 AC: 168 AN: 32406

American (AMR) AF: 0.0153 AC: 681 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.0341 AC: 878 AN: 25758

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39420

South Asian (SAS) AF: 0.00459 AC: 390 AN: 85058

European-Finnish (FIN) AF: 0.0195 AC: 1038 AN: 53298

Middle Eastern (MID) AF: 0.0285 AC: 161 AN: 5646

European-Non Finnish (NFE) AF: 0.0314 AC: 33291 AN: 1059546

Other (OTH) AF: 0.0257 AC: 1501 AN: 58444

GnomAD4 genome AF: 0.0222 AC: 3382 AN: 152202 Hom.: 59 Cov.: 33 AF XY: 0.0213 AC XY: 1584 AN XY: 74400

African (AFR) AF: 0.00561 AC: 233 AN: 41526

American (AMR) AF: 0.0203 AC: 310 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4828

European-Finnish (FIN) AF: 0.0213 AC: 226 AN: 10588

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0342 AC: 2323 AN: 68000

Other (OTH) AF: 0.0242 AC: 51 AN: 2108

Alfa AF: 0.0254 Hom.: 33

Bravo AF: 0.0217

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.4
DANN	Benign	0.76
PhyloP100		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11773535; hg19: chr7-112096043;