8-22689048-T-C

Variant names:

• chr8-22689048-T-C
• rs1877670
• NM_004430.3:c.*1425A>G

Variant summary

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

The NM_004430.3(EGR3):​c.*1425A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,554 control chromosomes in the GnomAD database, including 17,378 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 0.45 (17303 hom., cov: 33)
  • Exomes 𝑓: 0.60 (75 hom.)
• Consequence: EGR3 NM_004430.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.592 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.*1425A>G		3_prime_UTR	Exon 2 of 2	NP_004421.2
	EGR3	NM_001199880.2		c.*1425A>G		3_prime_UTR	Exon 2 of 2	NP_001186809.1
	EGR3	NM_001199881.2		c.*1425A>G		3_prime_UTR	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.*1425A>G		3_prime_UTR	Exon 2 of 2	ENSP00000318057.2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68842 AN: 152012 Hom.: 17294 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.603 AC: 257 AN: 426 Hom.: 75 Cov.: 0 AF XY: 0.602 AC XY: 154 AN XY: 256

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.607 AC: 255 AN: 420

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.453 AC: 68884 AN: 152128 Hom.: 17303 Cov.: 33 AF XY: 0.461 AC XY: 34295 AN XY: 74386

African (AFR) AF: 0.228 AC: 9447 AN: 41476

American (AMR) AF: 0.603 AC: 9222 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1962 AN: 3466

East Asian (EAS) AF: 0.416 AC: 2154 AN: 5182

South Asian (SAS) AF: 0.521 AC: 2512 AN: 4822

European-Finnish (FIN) AF: 0.596 AC: 6312 AN: 10586

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35612 AN: 67974

Other (OTH) AF: 0.483 AC: 1020 AN: 2112

Alfa AF: 0.500 Hom.: 19385

Bravo AF: 0.444

Asia WGS AF: 0.449 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.17
PhyloP100		-0.86
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: rs1877670; hg19: chr8-22546561;