15-78438807-C-T

Position:

• chr15-78438807-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320942.2(IREB2):​c.-202C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 170,510 control chromosomes in the GnomAD database, including 6,123 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 (5418 hom., cov: 31)
  • Exomes 𝑓: 0.26 (705 hom.)
• Consequence: IREB2 NM_001320942.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0790

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• 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/exons	MANE	Protein	UniProt
IREB2	NM_004136.4	c.19+451C>T		intron_variant		ENST00000258886.13	NP_004127.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IREB2	ENST00000258886.13	c.19+451C>T		intron_variant		1	NM_004136.4	ENSP00000258886.8

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35480 AN: 151906 Hom.: 5416 Cov.: 31

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.258 AC: 4768 AN: 18486 Hom.: 705 Cov.: 0 AF XY: 0.251 AC XY: 2457 AN XY: 9788

Gnomad4 AFR exome AF: 0.0586

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.0269

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.233 AC: 35486 AN: 152024 Hom.: 5418 Cov.: 31 AF XY: 0.231 AC XY: 17156 AN XY: 74302

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.254

Alfa AF: 0.248 Hom.: 1506

Bravo AF: 0.218

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs17405217; hg19: chr15-78731149;