rs17483929

Variant names:

• chr15-78450034-G-A
• rs17483929
• NM_004136.4:c.106+10153G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78450034-G-A
• chr15-78450034-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004136.4(IREB2):​c.106+10153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,024 control chromosomes in the GnomAD database, including 6,861 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 0.29 (6861 hom., cov: 33)
• Consequence: IREB2 NM_004136.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 30 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IREB2	NM_004136.4	c.106+10153G>A		intron_variant	Intron 2 of 21	ENST00000258886.13	NP_004127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IREB2	ENST00000258886.13	c.106+10153G>A		intron_variant	Intron 2 of 21	1	NM_004136.4	ENSP00000258886.8

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44420 AN: 151906 Hom.: 6852 Cov.: 33

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44469 AN: 152024 Hom.: 6861 Cov.: 33 AF XY: 0.290 AC XY: 21530 AN XY: 74296

African (AFR) AF: 0.221 AC: 9165 AN: 41450

American (AMR) AF: 0.280 AC: 4283 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1234 AN: 3468

East Asian (EAS) AF: 0.137 AC: 709 AN: 5172

South Asian (SAS) AF: 0.232 AC: 1121 AN: 4826

European-Finnish (FIN) AF: 0.318 AC: 3355 AN: 10544

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23514 AN: 67980

Other (OTH) AF: 0.304 AC: 643 AN: 2112

Alfa AF: 0.324 Hom.: 20767

Bravo AF: 0.287

Asia WGS AF: 0.199 AC: 694 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.61
PhyloP100		0.034
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17483929; hg19: chr15-78742376;