rs1042164

chr19-13153584-C-T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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]

(HGNC:):

ACMG classification

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	UniProt
IER2	NM_004907.3	c.398C>T	p.Ala133Val	missense_variant	2/2	ENST00000292433.4

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19070 AN: 152100 Hom.: 1705 Cov.: 32

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

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.: 33 AF XY: 0.161 AC XY: 116419 AN XY: 721182

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.: 32 AF XY: 0.127 AC XY: 9486 AN XY: 74416

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	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	12
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	N
MetaRNN	Benign	0.0043	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.63	N;N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.022
MPC		0.43
ClinPred		0.0022	T
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

Other links and lift over

dbSNP: rs1042164; hg19: chr19-13264398; COSMIC: COSV99460093; COSMIC: COSV99460093;