5-138466715-C-T

Variant names:

• chr5-138466715-C-T
• rs11743810
• NM_001964.3:c.308-42C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001964.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR1	NM_001964.3	MANE Select	c.308-42C>T		intron	N/A	NP_001955.1	P18146

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGR1	ENST00000239938.5	TSL:1 MANE Select	c.308-42C>T		intron	N/A	ENSP00000239938.4	P18146

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

GnomAD2 exomes AF: 0.496 AC: 111101 AN: 223794 AF XY: 0.491

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 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

African (AFR) AF: 0.330 AC: 10718 AN: 32492

American (AMR) AF: 0.561 AC: 23119 AN: 41202

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 12938 AN: 23384

East Asian (EAS) AF: 0.179 AC: 6998 AN: 39184

South Asian (SAS) AF: 0.354 AC: 28513 AN: 80610

European-Finnish (FIN) AF: 0.635 AC: 33017 AN: 51980

Middle Eastern (MID) AF: 0.433 AC: 2309 AN: 5328

European-Non Finnish (NFE) AF: 0.561 AC: 608905 AN: 1086356

Other (OTH) AF: 0.510 AC: 29786 AN: 58424

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

African (AFR) AF: 0.329 AC: 13630 AN: 41452

American (AMR) AF: 0.545 AC: 8331 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1948 AN: 3470

East Asian (EAS) AF: 0.167 AC: 865 AN: 5182

South Asian (SAS) AF: 0.348 AC: 1679 AN: 4822

European-Finnish (FIN) AF: 0.646 AC: 6819 AN: 10552

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38329 AN: 67906

Other (OTH) AF: 0.499 AC: 1051 AN: 2106

Alfa AF: 0.541 Hom.: 40846

Bravo AF: 0.468

Asia WGS AF: 0.284 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11743810; hg19: chr5-137802404; COSMIC: COSV53519186;