Variant 6-30744425-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003897.4(IER3):c.94G>A(p.Gly32Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000714 in 1,548,670 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00074 ( 1 hom. )

Consequence

IER3
NM_003897.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

IER3 (HGNC:5392): (immediate early response 3) This gene functions in the protection of cells from Fas- or tumor necrosis factor type alpha-induced apoptosis. Partially degraded and unspliced transcripts are found after virus infection in vitro, but these transcripts are not found in vivo and do not generate a valid protein. [provided by RefSeq, Jul 2008]

IER3 links:

HCG20 (HGNC:31334): (HLA complex group 20)

HCG20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028845578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IER3	NM_003897.4 linkuse as main transcript	c.94G>A	p.Gly32Ser	missense_variant	1/2	ENST00000259874.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IER3	ENST00000259874.6 linkuse as main transcript	c.94G>A	p.Gly32Ser	missense_variant	1/2	1	NM_003897.4	P1
HCG20	ENST00000656751.1 linkuse as main transcript	n.85+551C>T		intron_variant, non_coding_transcript_variant
IER3	ENST00000376377.2 linkuse as main transcript	c.94G>A	p.Gly32Ser	missense_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.000463

AC:

AN:

151306

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000812

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.000608

AC:

AN:

147910

Hom.:

AF XY:

0.000709

AC XY:

AN XY:

81854

show subpopulations

Gnomad AFR exome

AF:

0.000242

Gnomad AMR exome

AF:

0.000751

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000870

Gnomad SAS exome

AF:

0.0000480

Gnomad FIN exome

AF:

0.000673

Gnomad NFE exome

AF:

0.000951

Gnomad OTH exome

AF:

0.000507

GnomAD4 exome

AF:

0.000741

AC:

1036

AN:

1397242

Hom.:

Cov.:

AF XY:

0.000748

AC XY:

517

AN XY:

691468

show subpopulations

Gnomad4 AFR exome

AF:

0.0000649

Gnomad4 AMR exome

AF:

0.000741

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.000469

Gnomad4 NFE exome

AF:

0.000876

Gnomad4 OTH exome

AF:

0.000623

GnomAD4 genome

AF:

0.000462

AC:

AN:

151428

Hom.:

Cov.:

AF XY:

0.000351

AC XY:

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000812

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.000739

Hom.:

Bravo

AF:

0.000404

ESP6500AA

AF:

0.000390

AC:

ESP6500EA

AF:

0.00168

AC:

ExAC

AF:

0.000508

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2023

The c.94G>A (p.G32S) alteration is located in exon 1 (coding exon 1) of the IER3 gene. This alteration results from a G to A substitution at nucleotide position 94, causing the glycine (G) at amino acid position 32 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.84

.;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.029

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L

MutationTaster

Benign

0.93

N;N

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.0

D;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.41

MVP

0.52

MPC

2.1

ClinPred

0.098

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.26

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