rs1042164

Variant names:

• chr19-13153584-C-T
• rs1042164
• NM_004907.3:c.398C>T

Variant summary

Our verdict is Benign. The variant received -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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 31 publications found

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]

ENSG00000267598 (HGNC:58207):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
IER2	NM_004907.3	c.398C>T	p.Ala133Val	missense_variant	Exon 2 of 2	ENST00000292433.4	NP_004898.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IER2	ENST00000292433.4	c.398C>T	p.Ala133Val	missense_variant	Exon 2 of 2	1	NM_004907.3	ENSP00000292433.2

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

GnomAD2 exomes AF: 0.134 AC: 29775 AN: 222724 AF XY: 0.134

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 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

African (AFR) AF: 0.0314 AC: 1041 AN: 33116

American (AMR) AF: 0.0818 AC: 3533 AN: 43210

Ashkenazi Jewish (ASJ) AF: 0.0679 AC: 1754 AN: 25842

East Asian (EAS) AF: 0.0253 AC: 988 AN: 38996

South Asian (SAS) AF: 0.0761 AC: 6472 AN: 85076

European-Finnish (FIN) AF: 0.293 AC: 15207 AN: 51920

Middle Eastern (MID) AF: 0.0449 AC: 258 AN: 5748

European-Non Finnish (NFE) AF: 0.181 AC: 200258 AN: 1107072

Other (OTH) AF: 0.140 AC: 8364 AN: 59838

GnomAD4 genome AF: 0.125 AC: 19086 AN: 152218 Hom.: 1708 Cov.: 32 AF XY: 0.127 AC XY: 9486 AN XY: 74416

African (AFR) AF: 0.0374 AC: 1554 AN: 41558

American (AMR) AF: 0.0918 AC: 1404 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 244 AN: 3466

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5182

South Asian (SAS) AF: 0.0678 AC: 327 AN: 4826

European-Finnish (FIN) AF: 0.298 AC: 3149 AN: 10574

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11845 AN: 67998

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.145 Hom.: 6870

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
LIST_S2	Benign	0.51	.;.;T
MetaRNN	Benign	0.0043	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.63	N;N;N
PhyloP100		0.43
PrimateAI	Uncertain	0.51	T
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	T
GERP RS		0.60
Varity_R		0.11
gMVP		0.14
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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