Variant rs1042164 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004907.3(IER2):c.398C>T(p.Ala133Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,603,036 control chromosomes in the GnomAD database, including 23,441 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.13 ( 1708 hom., cov: 32)

Exomes 𝑓: 0.16 ( 21733 hom. )

Consequence

IER2
NM_004907.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.431

Variant links:

Genes affected

IER2 (HGNC:28871): (immediate early response 2) Predicted to enable DNA binding activity. Involved in cell motility and positive regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

IER2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042947233).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER2	NM_004907.3 linkuse as main transcript	c.398C>T	p.Ala133Val	missense_variant	2/2	ENST00000292433.4	NP_004898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IER2	ENST00000292433.4 linkuse as main transcript	c.398C>T	p.Ala133Val	missense_variant	2/2	1	NM_004907.3	ENSP00000292433	P1
	ENST00000592882.1 linkuse as main transcript	n.610G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19070

AN:

152100

Hom.:

1705

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0375

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.0911

Gnomad ASJ

AF:

0.0704

Gnomad EAS

AF:

0.0218

Gnomad SAS

AF:

0.0673

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.134

AC:

29775

AN:

222724

Hom.:

2677

AF XY:

0.134

AC XY:

16405

AN XY:

122284

show subpopulations

Gnomad AFR exome

AF:

0.0355

Gnomad AMR exome

AF:

0.0802

Gnomad ASJ exome

AF:

0.0696

Gnomad EAS exome

AF:

0.0191

Gnomad SAS exome

AF:

0.0759

Gnomad FIN exome

AF:

0.302

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.164

AC:

237875

AN:

1450818

Hom.:

21733

Cov.:

AF XY:

0.161

AC XY:

116419

AN XY:

721182

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.0818

Gnomad4 ASJ exome

AF:

0.0679

Gnomad4 EAS exome

AF:

0.0253

Gnomad4 SAS exome

AF:

0.0761

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.181

Gnomad4 OTH exome

AF:

0.140

GnomAD4 genome

AF:

0.125

AC:

19086

AN:

152218

Hom.:

1708

Cov.:

AF XY:

0.127

AC XY:

9486

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0374

Gnomad4 AMR

AF:

0.0918

Gnomad4 ASJ

AF:

0.0704

Gnomad4 EAS

AF:

0.0218

Gnomad4 SAS

AF:

0.0678

Gnomad4 FIN

AF:

0.298

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.151

Hom.:

4818

Bravo

AF:

0.106

TwinsUK

AF:

0.184

AC:

682

ALSPAC

AF:

0.186

AC:

716

ESP6500AA

AF:

0.0417

AC:

181

ESP6500EA

AF:

0.167

AC:

1425

ExAC

AF:

0.123

AC:

14818

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.51

.;.;T

MetaRNN

Benign

0.0043

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.63

N;N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.9

.;N;.

REVEL

Benign

0.044

Sift

Benign

0.15

.;T;.

Sift4G

Benign

0.16

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.022

MPC

0.43

ClinPred

0.0022

GERP RS

0.60

Varity_R

0.11

gMVP

0.14

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over