Variant 15-78494068-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004136.4(IREB2):c.2472+12A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,613,748 control chromosomes in the GnomAD database, including 798,977 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.97 ( 72065 hom., cov: 32)

Exomes 𝑓: 1.0 ( 726912 hom. )

Consequence

IREB2
NM_004136.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00800

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]

IREB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 15-78494068-A-C is Benign according to our data. Variant chr15-78494068-A-C is described in ClinVar as [Benign]. Clinvar id is 1300042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
IREB2	NM_004136.4 linkuse as main transcript	c.2472+12A>C	intron_variant	ENST00000258886.13
IREB2	NM_001320941.2 linkuse as main transcript	c.1722+12A>C	intron_variant
IREB2	NM_001320942.2 linkuse as main transcript	c.2301+12A>C	intron_variant
IREB2	NM_001354994.2 linkuse as main transcript	c.2301+12A>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IREB2	ENST00000258886.13 linkuse as main transcript	c.2472+12A>C		intron_variant		1	NM_004136.4	P1	P48200-1
IREB2	ENST00000558570.5 linkuse as main transcript	c.*1739+12A>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.972

AC:

147871

AN:

152156

Hom.:

72013

Cov.:

show subpopulations

Gnomad AFR

AF:

0.901

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.992

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.982

GnomAD3 exomes

AF:

0.993

AC:

248393

AN:

250114

Hom.:

123418

AF XY:

0.995

AC XY:

134919

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.901

Gnomad AMR exome

AF:

0.996

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

0.998

GnomAD4 exome

AF:

0.997

AC:

1457464

AN:

1461474

Hom.:

726912

Cov.:

AF XY:

0.998

AC XY:

725311

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.903

Gnomad4 AMR exome

AF:

0.995

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.994

GnomAD4 genome

AF:

0.972

AC:

147983

AN:

152274

Hom.:

72065

Cov.:

AF XY:

0.974

AC XY:

72488

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.901

Gnomad4 AMR

AF:

0.992

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.982

Alfa

AF:

0.996

Hom.:

72208

Bravo

AF:

0.968

Asia WGS

AF:

0.994

AC:

3455

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.88

DANN

Benign

0.57

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over