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GeneBe

7-112461856-T-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001550.4(IFRD1):c.568-10T>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 0.00131 in 1,395,098 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 10 hom. )

Consequence

IFRD1
NM_001550.4 splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0008750
2

Clinical Significance

Benign/Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.525
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-112461856-T-A is Benign according to our data. Variant chr7-112461856-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1284633.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-112461856-T-A is described in Lovd as [Benign]. Variant chr7-112461856-T-A is described in Lovd as [Likely_benign].
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IFRD1NM_001550.4 linkuse as main transcriptc.568-10T>A splice_polypyrimidine_tract_variant, intron_variant ENST00000403825.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IFRD1ENST00000403825.8 linkuse as main transcriptc.568-10T>A splice_polypyrimidine_tract_variant, intron_variant 1 NM_001550.4 P3O00458-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00116
AC:
175
AN:
150928
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000763
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00309
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00134
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00115
Gnomad OTH
AF:
0.000965
GnomAD3 exomes
AF:
0.00241
AC:
527
AN:
218924
Hom.:
6
AF XY:
0.00184
AC XY:
220
AN XY:
119526
show subpopulations
Gnomad AFR exome
AF:
0.000454
Gnomad AMR exome
AF:
0.0118
Gnomad ASJ exome
AF:
0.000109
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000440
Gnomad FIN exome
AF:
0.000929
Gnomad NFE exome
AF:
0.00117
Gnomad OTH exome
AF:
0.00132
GnomAD4 exome
AF:
0.00133
AC:
1659
AN:
1244056
Hom.:
10
Cov.:
20
AF XY:
0.00124
AC XY:
780
AN XY:
627572
show subpopulations
Gnomad4 AFR exome
AF:
0.000867
Gnomad4 AMR exome
AF:
0.00983
Gnomad4 ASJ exome
AF:
0.0000820
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000470
Gnomad4 FIN exome
AF:
0.00115
Gnomad4 NFE exome
AF:
0.00114
Gnomad4 OTH exome
AF:
0.00118
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00116
AC:
175
AN:
151042
Hom.:
1
Cov.:
32
AF XY:
0.00102
AC XY:
75
AN XY:
73862
show subpopulations
Gnomad4 AFR
AF:
0.000761
Gnomad4 AMR
AF:
0.00309
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00134
Gnomad4 NFE
AF:
0.00115
Gnomad4 OTH
AF:
0.000955
Alfa
AF:
0.00169
Hom.:
0
Bravo
AF:
0.00170

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
not provided Benign:1
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
Cadd
Benign
1.2
Dann
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00088
dbscSNV1_RF
Benign
0.066
SpliceAI score (max)
0.070
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs565300368; hg19: chr7-112101911; COSMIC: COSV50043686; COSMIC: COSV50043686; API