GeneBe

rs1062980

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004136.4(IREB2):​c.*2042T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Failed GnomAD Quality Control

Consequence

IREB2
NM_004136.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.594

Publications

0 publications found
Variant links:
Genes affected
IREB2 (HGNC:6115): (iron responsive element binding protein 2) The protein encoded by this gene is an RNA-binding protein that acts to regulate iron levels in the cells by regulating the translation and stability of mRNAs that affect iron homeostasis under conditions when iron is depleted. When iron levels are low, this protein binds to iron-responsive elements (IRES), stem-loop structures located either in the 5' or 3' UTRs. Binding to the 5' UTR represses translation, while binding to the 3' UTR inhibits mRNA degradation. When iron is found in the cell, this protein is degraded in a F-box and leucine rich repeat protein 5-dependent manner. Variants in this gene have been associated with lung cancer and chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2017]
IREB2 Gene-Disease associations (from GenCC):
  • neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia
    Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IREB2NM_004136.4 linkc.*2042T>A 3_prime_UTR_variant Exon 22 of 22 ENST00000258886.13 NP_004127.2
IREB2NM_001320942.2 linkc.*2042T>A 3_prime_UTR_variant Exon 22 of 22 NP_001307871.2
IREB2NM_001354994.2 linkc.*2042T>A 3_prime_UTR_variant Exon 22 of 22 NP_001341923.2
IREB2NM_001320941.2 linkc.*2042T>A 3_prime_UTR_variant Exon 21 of 21 NP_001307870.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IREB2ENST00000258886.13 linkc.*2042T>A 3_prime_UTR_variant Exon 22 of 22 1 NM_004136.4 ENSP00000258886.8

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
151886
Hom.:
0
Cov.:
31
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
151886
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74168
African (AFR)
AF:
0.00
AC:
0
AN:
41346
American (AMR)
AF:
0.00
AC:
0
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5174
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10546
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67970
Other (OTH)
AF:
0.00
AC:
0
AN:
2080

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.6
DANN
Benign
0.65
PhyloP100
-0.59

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

Other links and lift over

dbSNP: rs1062980; hg19: chr15-78792527; API