rs17483548

Variant names:

• chr15-78437971-G-A
• rs17483548
• NM_001354994.2:c.-153+250G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78437971-G-A
• chr15-78437971-G-C

Variant summary

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

The NM_001354994.2(IREB2):​c.-153+250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,190 control chromosomes in the GnomAD database, including 5,431 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 0.23 (5431 hom., cov: 33)
• Consequence: IREB2 NM_001354994.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 28 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=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IREB2	NM_001354994.2	c.-153+250G>A		intron_variant	Intron 1 of 21		NP_001341923.2
IREB2	NM_004136.4	c.-367G>A		upstream_gene_variant		ENST00000258886.13	NP_004127.2
IREB2	NM_001320941.2	c.-1047G>A		upstream_gene_variant			NP_001307870.2
IREB2	NM_001320943.2	c.-367G>A		upstream_gene_variant			NP_001307872.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IREB2	ENST00000560840.5	c.-153+250G>A		intron_variant	Intron 1 of 3	5		ENSP00000453172.1
IREB2	ENST00000258886.13	c.-367G>A		upstream_gene_variant		1	NM_004136.4	ENSP00000258886.8
IREB2	ENST00000559215.5	n.-367G>A		upstream_gene_variant		4		ENSP00000453532.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35682 AN: 152072 Hom.: 5429 Cov.: 33

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.0398

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.235 AC: 35691 AN: 152190 Hom.: 5431 Cov.: 33 AF XY: 0.232 AC XY: 17259 AN XY: 74390

African (AFR) AF: 0.0595 AC: 2473 AN: 41564

American (AMR) AF: 0.221 AC: 3382 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1196 AN: 3468

East Asian (EAS) AF: 0.0400 AC: 207 AN: 5170

South Asian (SAS) AF: 0.211 AC: 1018 AN: 4828

European-Finnish (FIN) AF: 0.314 AC: 3317 AN: 10570

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23123 AN: 67980

Other (OTH) AF: 0.256 AC: 540 AN: 2112

Alfa AF: 0.278 Hom.: 2829

Bravo AF: 0.219

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	2.3
DANN	Benign	0.81
PhyloP100		-0.42
PromoterAI		-0.14	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17483548; hg19: chr15-78730313;