8-22689048-T-C

Position:

• chr8-22689048-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGR3	NM_004430.3	c.*1425A>G		3_prime_UTR_variant	2/2	ENST00000317216.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR3	ENST00000317216.3	c.*1425A>G		3_prime_UTR_variant	2/2	1	NM_004430.3	P2

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

Gnomad4 FIN exome AF: 0.607

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.250

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

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.566

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.483

Alfa AF: 0.499 Hom.: 16092

Bravo AF: 0.444

Asia WGS AF: 0.449 AC: 1560 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.48
DANN	Benign	0.17

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: rs1877670; hg19: chr8-22546561;