rs11639224

Variant names:

• chr15-78461029-A-G
• rs11639224
• NM_004136.4:c.107-1893A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-78461029-A-G
• chr15-78461029-A-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.107-1893A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,928 control chromosomes in the GnomAD database, including 10,832 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 (10832 hom., cov: 31)
• Consequence: IREB2 NM_004136.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IREB2	NM_004136.4	c.107-1893A>G		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.107-1893A>G		intron_variant	Intron 2 of 21	1	NM_004136.4	ENSP00000258886.8

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55403 AN: 151808 Hom.: 10830 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.365 AC: 55424 AN: 151928 Hom.: 10832 Cov.: 31 AF XY: 0.367 AC XY: 27236 AN XY: 74274

African (AFR) AF: 0.225 AC: 9334 AN: 41424

American (AMR) AF: 0.327 AC: 4990 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1400 AN: 3472

East Asian (EAS) AF: 0.475 AC: 2450 AN: 5160

South Asian (SAS) AF: 0.405 AC: 1950 AN: 4820

European-Finnish (FIN) AF: 0.431 AC: 4543 AN: 10534

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29461 AN: 67946

Other (OTH) AF: 0.372 AC: 785 AN: 2110

Alfa AF: 0.291 Hom.: 1109

Bravo AF: 0.354

Asia WGS AF: 0.400 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.98
DANN	Benign	0.84
PhyloP100		0.50
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: rs11639224; hg19: chr15-78753371;