rs11743810

Positions:

• chr5-138466715-C-T

Variant summary

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

The NM_001964.3(EGR1):​c.308-42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,570,944 control chromosomes in the GnomAD database, including 226,660 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 0.48 (18956 hom., cov: 32)
  • Exomes 𝑓: 0.53 (207704 hom.)
• Consequence: EGR1 NM_001964.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179

Genes affected

EGR1 (HGNC:3238): (early growth response 1) The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentitation and mitogenesis. Studies suggest this is a cancer suppressor gene. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGR1	NM_001964.3	c.308-42C>T		intron_variant		ENST00000239938.5	NP_001955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGR1	ENST00000239938.5	c.308-42C>T		intron_variant		1	NM_001964.3	ENSP00000239938.4

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73159 AN: 151862 Hom.: 18947 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.502

GnomAD3 exomes AF: 0.496 AC: 111101 AN: 223794 Hom.: 29864 AF XY: 0.491 AC XY: 58945 AN XY: 119956

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.559

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.346

Gnomad FIN exome AF: 0.640

Gnomad NFE exome AF: 0.563

Gnomad OTH exome AF: 0.514

GnomAD4 exome AF: 0.533 AC: 756303 AN: 1418960 Hom.: 207704 Cov.: 35 AF XY: 0.528 AC XY: 369631 AN XY: 700122

Gnomad4 AFR exome AF: 0.330

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.354

Gnomad4 FIN exome AF: 0.635

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.510

GnomAD4 genome AF: 0.482 AC: 73200 AN: 151984 Hom.: 18956 Cov.: 32 AF XY: 0.482 AC XY: 35811 AN XY: 74298

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.545

Gnomad4 ASJ AF: 0.561

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.499

Alfa AF: 0.539 Hom.: 32281

Bravo AF: 0.468

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11743810; hg19: chr5-137802404; COSMIC: COSV53519186;