NM_005228.5:c.2487G>A

Variant names:

• chr7-55191736-G-A
• rs41420046
• NM_005228.5:c.2487G>A

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_005228.5(EGFR):​c.2487G>A​(p.Glu829Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,613,956 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: EGFR NM_005228.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.679
• Publications: 6 publications found

Genes affected

EGFR (HGNC:3236): (epidermal growth factor receptor) The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor, thus inducing receptor dimerization and tyrosine autophosphorylation leading to cell proliferation. Mutations in this gene are associated with lung cancer. EGFR is a component of the cytokine storm which contributes to a severe form of Coronavirus Disease 2019 (COVID-19) resulting from infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). [provided by RefSeq, Jul 2020]

EGFR-AS1 (HGNC:40207): (EGFR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 7-55191736-G-A is Benign according to our data. Variant chr7-55191736-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.679 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00189 (287/152226) while in subpopulation AFR AF = 0.00645 (268/41528). AF 95% confidence interval is 0.00582. There are 1 homozygotes in GnomAd4. There are 146 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005228.5. 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
	EGFR	NM_005228.5	MANE Select	c.2487G>A	p.Glu829Glu	synonymous	Exon 21 of 28	NP_005219.2
	EGFR	NM_001346899.2		c.2352G>A	p.Glu784Glu	synonymous	Exon 20 of 27	NP_001333828.1
	EGFR	NM_001346900.2		c.2328G>A	p.Glu776Glu	synonymous	Exon 21 of 28	NP_001333829.1	C9JYS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2487G>A	p.Glu829Glu	synonymous	Exon 21 of 28	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.2352G>A	p.Glu784Glu	synonymous	Exon 20 of 26	ENSP00000415559.1	Q504U8
	EGFR	ENST00000898199.1		c.2478G>A	p.Glu826Glu	synonymous	Exon 21 of 28	ENSP00000568258.1

Frequencies

GnomAD3 genomes AF: 0.00188 AC: 286 AN: 152108 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00645

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000637 AC: 160 AN: 251060 AF XY: 0.000560

Gnomad AFR exome AF: 0.00795

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000232 AC: 339 AN: 1461730 Hom.: 1 Cov.: 31 AF XY: 0.000212 AC XY: 154 AN XY: 727172

African (AFR) AF: 0.00783 AC: 262 AN: 33476

American (AMR) AF: 0.000581 AC: 26 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53282

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1112002

Other (OTH) AF: 0.000397 AC: 24 AN: 60390

GnomAD4 genome AF: 0.00189 AC: 287 AN: 152226 Hom.: 1 Cov.: 32 AF XY: 0.00196 AC XY: 146 AN XY: 74414

African (AFR) AF: 0.00645 AC: 268 AN: 41528

American (AMR) AF: 0.000588 AC: 9 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

Alfa AF: 0.000713 Hom.: 1

Bravo AF: 0.00215

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	2	Lung cancer (2)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	EGFR-related lung cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	3.9
DANN	Benign	0.86
PhyloP100		0.68
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=90/10	polymorphism

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: rs41420046; hg19: chr7-55259429; COSMIC: COSV51796834;