7-112461854-T-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001550.4(IFRD1):c.568-12T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 1,190,456 control chromosomes in the GnomAD database, including 246,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.73 (34129 hom., cov: 29)
  • Exomes 𝑓: 0.66 (212867 hom.)
• Consequence: IFRD1 NM_001550.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005965
• Clinical Significance: Benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.424

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-112461854-T-A is Benign according to our data. Variant chr7-112461854-T-A is described in ClinVar as [Benign]. Clinvar id is 1284337.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-112461854-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFRD1	NM_001550.4	c.568-12T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000403825.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFRD1	ENST00000403825.8	c.568-12T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001550.4	P3

Frequencies

GnomAD3 genomes AF: 0.725 AC: 100257 AN: 138240 Hom.: 34113 Cov.: 29

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.833

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.733

GnomAD3 exomes AF: 0.589 AC: 110848 AN: 188114 Hom.: 29617 AF XY: 0.586 AC XY: 60049 AN XY: 102518

Gnomad AFR exome AF: 0.697

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.594

Gnomad EAS exome AF: 0.282

Gnomad SAS exome AF: 0.434

Gnomad FIN exome AF: 0.639

Gnomad NFE exome AF: 0.670

Gnomad OTH exome AF: 0.616

GnomAD4 exome AF: 0.661 AC: 695895 AN: 1052110 Hom.: 212867 Cov.: 16 AF XY: 0.658 AC XY: 348782 AN XY: 530212

Gnomad4 AFR exome AF: 0.697

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.202

Gnomad4 SAS exome AF: 0.536

Gnomad4 FIN exome AF: 0.671

Gnomad4 NFE exome AF: 0.691

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.725 AC: 100326 AN: 138346 Hom.: 34129 Cov.: 29 AF XY: 0.717 AC XY: 48196 AN XY: 67210

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.736

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.730

Alfa AF: 0.687 Hom.: 3342

Bravo AF: 0.662

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	-0.81
Cadd	Benign	2.5
Dann	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000060
dbscSNV1_RF	Benign	0.014
SpliceAI score (max)		0.040		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: rs2708609; hg19: chr7-112101909; COSMIC: COSV50044223; COSMIC: COSV50044223;