rs35201266

Positions:

• chr8-22692184-C-T

Variant summary

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

The NM_004430.3(EGR3):​c.154+607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,387,582 control chromosomes in the GnomAD database, including 57,221 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 0.27 (5947 hom., cov: 33)
  • Exomes 𝑓: 0.28 (51274 hom.)
• Consequence: EGR3 NM_004430.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.392

Genes affected

EGR3 (HGNC:3240): (early growth response 3) This gene encodes a transcriptional regulator that belongs to the EGR family of C2H2-type zinc-finger proteins. It is an immediate-early growth response gene which is induced by mitogenic stimulation. The protein encoded by this gene participates in the transcriptional regulation of genes in controling biological rhythm. It may also play a role in a wide variety of processes including muscle development, lymphocyte development, endothelial cell growth and migration, and neuronal development. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Dec 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.41 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGR3	NM_004430.3	c.154+607G>A		intron_variant		ENST00000317216.3	NP_004421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGR3	ENST00000317216.3	c.154+607G>A		intron_variant		1	NM_004430.3	ENSP00000318057	P2
	ENST00000523627.1	n.164+1871C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40986 AN: 152042 Hom.: 5942 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.313

GnomAD4 exome AF: 0.285 AC: 351831 AN: 1235422 Hom.: 51274 Cov.: 34 AF XY: 0.285 AC XY: 170921 AN XY: 598882

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.365

Gnomad4 EAS exome AF: 0.317

Gnomad4 SAS exome AF: 0.282

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.289

GnomAD4 genome AF: 0.270 AC: 41016 AN: 152160 Hom.: 5947 Cov.: 33 AF XY: 0.271 AC XY: 20180 AN XY: 74388

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.376

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.311

Alfa AF: 0.271 Hom.: 738

Bravo AF: 0.277

Asia WGS AF: 0.266 AC: 924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.91

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: rs35201266; hg19: chr8-22549697;