chr6-30743580-G-A

Position:

• chr6-30743580-G-A

Variant summary

Our verdict is Benign. Variant got -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

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)

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IER3	NM_003897.4	c.*356C>T		3_prime_UTR_variant	2/2	ENST00000259874.6	NP_003888.2
IER3-AS1	NR_149095.1	n.481G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IER3	ENST00000259874.6	c.*356C>T		3_prime_UTR_variant	2/2	1	NM_003897.4	ENSP00000259874	P1
IER3-AS1	ENST00000702432.1	n.514G>A		non_coding_transcript_exon_variant	2/2

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

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0605

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.146

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

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0710

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.138

Alfa AF: 0.163 Hom.: 2735

Bravo AF: 0.120

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.93
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8512; hg19: chr6-30711357;