rs2229294

Positions:

• chr2-73291405-G-A

Variant summary

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

The NM_001965.4(EGR4):​c.*52C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,527,060 control chromosomes in the GnomAD database, including 15,401 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 0.18 (3886 hom., cov: 33)
  • Exomes 𝑓: 0.094 (11515 hom.)
• Consequence: EGR4 NM_001965.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623

Genes affected

EGR4 (HGNC:3241): (early growth response 4) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGR4	NM_001965.4	c.*52C>T		3_prime_UTR_variant	2/2	ENST00000436467.4
EGR4	XM_047443603.1	c.*52C>T		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGR4	ENST00000436467.4	c.*52C>T		3_prime_UTR_variant	2/2	1	NM_001965.4	P2
EGR4	ENST00000545030.1	c.*52C>T		3_prime_UTR_variant	2/2	1		A2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26737 AN: 152098 Hom.: 3873 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.0626

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.0601

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.0944 AC: 129848 AN: 1374842 Hom.: 11515 Cov.: 31 AF XY: 0.0963 AC XY: 64975 AN XY: 674382

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.441

Gnomad4 SAS exome AF: 0.217

Gnomad4 FIN exome AF: 0.0547

Gnomad4 NFE exome AF: 0.0612

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.176 AC: 26789 AN: 152218 Hom.: 3886 Cov.: 33 AF XY: 0.178 AC XY: 13223 AN XY: 74416

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0554

Gnomad4 NFE AF: 0.0601

Gnomad4 OTH AF: 0.166

Alfa AF: 0.124 Hom.: 353

Bravo AF: 0.198

Asia WGS AF: 0.323 AC: 1123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.9
DANN	Benign	0.83

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: rs2229294; hg19: chr2-73518533; COSMIC: COSV71531991;