2-73291405-G-T

Variant names:

• chr2-73291405-G-T
• rs2229294
• NM_001965.4:c.*52C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001965.4(EGR4):​c.*52C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,375,050 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: EGR4 NM_001965.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.623
• Publications: 0 publications found

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]

ENSG00000310032 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGR4	NM_001965.4	c.*52C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000436467.4	NP_001956.4
EGR4	XM_047443603.1	c.*52C>A		3_prime_UTR_variant	Exon 2 of 2		XP_047299559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGR4	ENST00000436467.4	c.*52C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_001965.4	ENSP00000419687.1
EGR4	ENST00000545030.1	c.*52C>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000445626.1
ENSG00000310032	ENST00000846694.1	n.174-7161G>T		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1375050 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 674486

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30592

American (AMR) AF: 0.00 AC: 0 AN: 32106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20740

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38794

South Asian (SAS) AF: 0.00 AC: 0 AN: 71670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4362

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071368

Other (OTH) AF: 0.00 AC: 0 AN: 56498

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.69
PhyloP100		0.62

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: rs2229294; hg19: chr2-73518533;