chr8-22691277-G-T

Variant names:

• chr8-22691277-G-T
• rs3750192
• NM_004430.3:c.360C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004430.3(EGR3):​c.360C>A​(p.Leu120Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.0827 in 1,613,898 control chromosomes in the GnomAD database, including 6,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (578 hom., cov: 33)
  • Exomes 𝑓: 0.082 (5700 hom.)
• Consequence: EGR3 NM_004430.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.77
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 8-22691277-G-T is Benign according to our data. Variant chr8-22691277-G-T is described in ClinVar as Benign. ClinVar VariationId is 1287186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 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.360C>A	p.Leu120Leu	synonymous	Exon 2 of 2	NP_004421.2
	EGR3	NM_001199880.2		c.246C>A	p.Leu82Leu	synonymous	Exon 2 of 2	NP_001186809.1
	EGR3	NM_001199881.2		c.198C>A	p.Leu66Leu	synonymous	Exon 2 of 2	NP_001186810.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR3	ENST00000317216.3	TSL:1 MANE Select	c.360C>A	p.Leu120Leu	synonymous	Exon 2 of 2	ENSP00000318057.2
	EGR3	ENST00000522910.1	TSL:2	c.246C>A	p.Leu82Leu	synonymous	Exon 2 of 2	ENSP00000430310.1
	EGR3	ENST00000518773.1	TSL:4	n.393C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 12915 AN: 152106 Hom.: 578 Cov.: 33

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.0819

Gnomad FIN AF: 0.0849

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0919

GnomAD2 exomes AF: 0.0961 AC: 24012 AN: 249842 AF XY: 0.0917

Gnomad AFR exome AF: 0.0831

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.0499

Gnomad EAS exome AF: 0.199

Gnomad FIN exome AF: 0.0814

Gnomad NFE exome AF: 0.0770

Gnomad OTH exome AF: 0.0860

GnomAD4 exome AF: 0.0824 AC: 120486 AN: 1461674 Hom.: 5700 Cov.: 32 AF XY: 0.0817 AC XY: 59414 AN XY: 727128

African (AFR) AF: 0.0849 AC: 2841 AN: 33480

American (AMR) AF: 0.146 AC: 6538 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 1256 AN: 26134

East Asian (EAS) AF: 0.230 AC: 9118 AN: 39700

South Asian (SAS) AF: 0.0759 AC: 6550 AN: 86258

European-Finnish (FIN) AF: 0.0865 AC: 4605 AN: 53240

Middle Eastern (MID) AF: 0.0531 AC: 306 AN: 5768

European-Non Finnish (NFE) AF: 0.0759 AC: 84437 AN: 1111996

Other (OTH) AF: 0.0801 AC: 4835 AN: 60388

GnomAD4 genome AF: 0.0849 AC: 12923 AN: 152224 Hom.: 578 Cov.: 33 AF XY: 0.0853 AC XY: 6353 AN XY: 74438

African (AFR) AF: 0.0821 AC: 3413 AN: 41550

American (AMR) AF: 0.104 AC: 1586 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1063 AN: 5168

South Asian (SAS) AF: 0.0818 AC: 395 AN: 4830

European-Finnish (FIN) AF: 0.0849 AC: 900 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5206 AN: 67980

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.0797 Hom.: 524

Bravo AF: 0.0893

Asia WGS AF: 0.143 AC: 498 AN: 3478

EpiCase AF: 0.0759

EpiControl AF: 0.0730

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		3.8
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: rs3750192; hg19: chr8-22548790; COSMIC: COSV57834559;