rs2568494

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004136.4(IREB2):​c.106+8741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 152,064 control chromosomes in the GnomAD database, including 10,112 homozygotes. 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 0.36 ( 10112 hom., cov: 33)

Consequence

IREB2
NM_004136.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.18
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IREB2NM_004136.4 linkuse as main transcriptc.106+8741G>A intron_variant ENST00000258886.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IREB2ENST00000258886.13 linkuse as main transcriptc.106+8741G>A intron_variant 1 NM_004136.4 P1P48200-1

Frequencies

GnomAD3 genomes
AF:
0.358
AC:
54366
AN:
151944
Hom.:
10105
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.441
Gnomad AMI
AF:
0.371
Gnomad AMR
AF:
0.308
Gnomad ASJ
AF:
0.383
Gnomad EAS
AF:
0.160
Gnomad SAS
AF:
0.235
Gnomad FIN
AF:
0.317
Gnomad MID
AF:
0.424
Gnomad NFE
AF:
0.347
Gnomad OTH
AF:
0.348
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.358
AC:
54415
AN:
152064
Hom.:
10112
Cov.:
33
AF XY:
0.353
AC XY:
26222
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.440
Gnomad4 AMR
AF:
0.308
Gnomad4 ASJ
AF:
0.383
Gnomad4 EAS
AF:
0.161
Gnomad4 SAS
AF:
0.237
Gnomad4 FIN
AF:
0.317
Gnomad4 NFE
AF:
0.347
Gnomad4 OTH
AF:
0.345
Alfa
AF:
0.350
Hom.:
9349
Bravo
AF:
0.361
Asia WGS
AF:
0.219
AC:
765
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
6.2
DANN
Benign
0.38

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

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

Other links and lift over

dbSNP: rs2568494; hg19: chr15-78740964; API