7-112456018-T-C

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.216T>C(p.Asp72=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,603,350 control chromosomes in the GnomAD database, including 2,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.039 (163 hom., cov: 33)
  • Exomes 𝑓: 0.057 (2745 hom.)
• Consequence: IFRD1 NM_001550.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:2
• Conservation: PhyloP100: 1.09

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=-0.61).
• BP6: Variant 7-112456018-T-C is Benign according to our data. Variant chr7-112456018-T-C is described in ClinVar as [Benign]. Clinvar id is 1284482.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-112456018-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFRD1	NM_001550.4	c.216T>C	p.Asp72=	synonymous_variant	3/12	ENST00000403825.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFRD1	ENST00000403825.8	c.216T>C	p.Asp72=	synonymous_variant	3/12	1	NM_001550.4	P3

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5926 AN: 152166 Hom.: 163 Cov.: 33

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.0341

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0569

Gnomad OTH AF: 0.0336

GnomAD3 exomes AF: 0.0473 AC: 11894 AN: 251236 Hom.: 392 AF XY: 0.0502 AC XY: 6823 AN XY: 135818

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.0177

Gnomad ASJ exome AF: 0.0339

Gnomad EAS exome AF: 0.0631

Gnomad SAS exome AF: 0.0799

Gnomad FIN exome AF: 0.0251

Gnomad NFE exome AF: 0.0561

Gnomad OTH exome AF: 0.0377

GnomAD4 exome AF: 0.0569 AC: 82552 AN: 1451066 Hom.: 2745 Cov.: 28 AF XY: 0.0577 AC XY: 41712 AN XY: 722696

Gnomad4 AFR exome AF: 0.00914

Gnomad4 AMR exome AF: 0.0192

Gnomad4 ASJ exome AF: 0.0328

Gnomad4 EAS exome AF: 0.0489

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.0264

Gnomad4 NFE exome AF: 0.0606

Gnomad4 OTH exome AF: 0.0576

GnomAD4 genome AF: 0.0389 AC: 5925 AN: 152284 Hom.: 163 Cov.: 33 AF XY: 0.0382 AC XY: 2841 AN XY: 74466

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0227

Gnomad4 ASJ AF: 0.0341

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.0775

Gnomad4 FIN AF: 0.0251

Gnomad4 NFE AF: 0.0569

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0473 Hom.: 104

Bravo AF: 0.0364

Asia WGS AF: 0.0650 AC: 226 AN: 3476

EpiCase AF: 0.0532

EpiControl AF: 0.0528

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.3
Dann	Benign	0.69
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

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

Publications

LitVar

Other links and lift over

dbSNP: rs34349457; hg19: chr7-112096073;