8-22692184-C-T

Variant names:

• chr8-22692184-C-T
• rs35201266
• NM_004430.3:c.154+607G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ENSG00000253125 (HGNC:58186):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004430.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR3	NM_004430.3	MANE Select	c.154+607G>A		intron	N/A	NP_004421.2
	EGR3	NM_001199880.2		c.40+118G>A		intron	N/A	NP_001186809.1
	EGR3	NM_001199881.2		c.-9+315G>A		intron	N/A	NP_001186810.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR3	ENST00000317216.3	TSL:1 MANE Select	c.154+607G>A		intron	N/A	ENSP00000318057.2
	EGR3	ENST00000518773.1	TSL:4	n.41G>A		non_coding_transcript_exon	Exon 1 of 2
	EGR3	ENST00000522910.1	TSL:2	c.40+118G>A		intron	N/A	ENSP00000430310.1

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

African (AFR) AF: 0.174 AC: 4246 AN: 24466

American (AMR) AF: 0.498 AC: 7390 AN: 14848

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 6510 AN: 17814

East Asian (EAS) AF: 0.317 AC: 8984 AN: 28324

South Asian (SAS) AF: 0.282 AC: 16553 AN: 58732

European-Finnish (FIN) AF: 0.269 AC: 7862 AN: 29194

Middle Eastern (MID) AF: 0.359 AC: 1377 AN: 3832

European-Non Finnish (NFE) AF: 0.282 AC: 284204 AN: 1007396

Other (OTH) AF: 0.289 AC: 14705 AN: 50816

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

African (AFR) AF: 0.173 AC: 7175 AN: 41548

American (AMR) AF: 0.418 AC: 6395 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1304 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1424 AN: 5156

South Asian (SAS) AF: 0.268 AC: 1292 AN: 4828

European-Finnish (FIN) AF: 0.268 AC: 2841 AN: 10602

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19540 AN: 67940

Other (OTH) AF: 0.311 AC: 657 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.91
PhyloP100		0.39
PromoterAI		-0.038	Neutral
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: rs35201266; hg19: chr8-22549697;