7-112462300-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001550.4(IFRD1):c.828T>G(p.Ser276=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,611,978 control chromosomes in the GnomAD database, including 46,144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.26 (5469 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40675 hom.)
• Consequence: IFRD1 NM_001550.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:2
• Conservation: PhyloP100: 1.56

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 7-112462300-T-G is Benign according to our data. Variant chr7-112462300-T-G is described in ClinVar as [Benign]. Clinvar id is 1284350.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-112462300-T-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFRD1	NM_001550.4	c.828T>G	p.Ser276=	synonymous_variant	8/12	ENST00000403825.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFRD1	ENST00000403825.8	c.828T>G	p.Ser276=	synonymous_variant	8/12	1	NM_001550.4	P3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39902 AN: 152006 Hom.: 5467 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.271

GnomAD3 exomes AF: 0.236 AC: 59166 AN: 251074 Hom.: 7249 AF XY: 0.235 AC XY: 31852 AN XY: 135688

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.172

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.192

Gnomad SAS exome AF: 0.203

Gnomad FIN exome AF: 0.292

Gnomad NFE exome AF: 0.241

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.233 AC: 340702 AN: 1459854 Hom.: 40675 Cov.: 33 AF XY: 0.233 AC XY: 169008 AN XY: 726346

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.271

Gnomad4 EAS exome AF: 0.181

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.263 AC: 39935 AN: 152124 Hom.: 5469 Cov.: 32 AF XY: 0.261 AC XY: 19375 AN XY: 74334

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.258

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.269

Alfa AF: 0.243 Hom.: 9205

Bravo AF: 0.261

Asia WGS AF: 0.216 AC: 752 AN: 3478

EpiCase AF: 0.246

EpiControl AF: 0.248

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	9.1
Dann	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2253962; hg19: chr7-112102355; COSMIC: COSV50044034; COSMIC: COSV50044034;