NM_003897.4:c.*356C>T

Variant names:

• chr6-30743580-G-A
• rs8512
• NM_003897.4:c.*356C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003897.4(IER3):​c.*356C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 307,298 control chromosomes in the GnomAD database, including 3,922 homozygotes. In-silico tool predicts 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 (1635 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2287 hom.)
• Consequence: IER3 NM_003897.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724
• Publications: 15 publications found

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-AS1 (HGNC:53629): (IER3 antisense RNA 1)

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003897.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IER3	NM_003897.4	MANE Select	c.*356C>T		3_prime_UTR	Exon 2 of 2	NP_003888.2
	IER3-AS1	NR_149095.1		n.481G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IER3	ENST00000259874.6	TSL:1 MANE Select	c.*356C>T		3_prime_UTR	Exon 2 of 2	ENSP00000259874.5
	IER3	ENST00000917877.1		c.*356C>T		3_prime_UTR	Exon 2 of 2	ENSP00000587936.1
	IER3	ENST00000376377.2	TSL:6	c.*522C>T		3_prime_UTR	Exon 1 of 1	ENSP00000365557.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19667 AN: 152062 Hom.: 1634 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.139

GnomAD4 exome AF: 0.158 AC: 24547 AN: 155118 Hom.: 2287 Cov.: 0 AF XY: 0.161 AC XY: 12866 AN XY: 79704

African (AFR) AF: 0.0268 AC: 115 AN: 4290

American (AMR) AF: 0.166 AC: 621 AN: 3752

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 645 AN: 5914

East Asian (EAS) AF: 0.0605 AC: 603 AN: 9970

South Asian (SAS) AF: 0.227 AC: 2632 AN: 11574

European-Finnish (FIN) AF: 0.185 AC: 1372 AN: 7434

Middle Eastern (MID) AF: 0.169 AC: 145 AN: 858

European-Non Finnish (NFE) AF: 0.167 AC: 16904 AN: 100952

Other (OTH) AF: 0.146 AC: 1510 AN: 10374

GnomAD4 genome AF: 0.129 AC: 19676 AN: 152180 Hom.: 1635 Cov.: 32 AF XY: 0.132 AC XY: 9852 AN XY: 74398

African (AFR) AF: 0.0313 AC: 1300 AN: 41534

American (AMR) AF: 0.160 AC: 2444 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 368 AN: 3468

East Asian (EAS) AF: 0.0710 AC: 368 AN: 5180

South Asian (SAS) AF: 0.224 AC: 1078 AN: 4808

European-Finnish (FIN) AF: 0.191 AC: 2021 AN: 10594

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11547 AN: 67996

Other (OTH) AF: 0.138 AC: 290 AN: 2106

Alfa AF: 0.155 Hom.: 6644

Bravo AF: 0.120

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	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: rs8512; hg19: chr6-30711357;