chr7-55179895-G-A

Variant names:

• chr7-55179895-G-A
• rs845558
• NM_005228.5:c.2284-1398G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.2284-1398G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,102 control chromosomes in the GnomAD database, including 14,624 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 0.43 (14624 hom., cov: 33)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890
• Publications: 23 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.2284-1398G>A		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.2149-1398G>A		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.2125-1398G>A		intron	N/A	NP_001333829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2284-1398G>A		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.2149-1398G>A		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000898199.1		c.2275-1398G>A		intron	N/A	ENSP00000568258.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64836 AN: 151970 Hom.: 14605 Cov.: 33

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.125 AC: 2 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.200 AC: 2 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.427 AC: 64899 AN: 152086 Hom.: 14624 Cov.: 33 AF XY: 0.413 AC XY: 30717 AN XY: 74332

African (AFR) AF: 0.509 AC: 21109 AN: 41486

American (AMR) AF: 0.438 AC: 6703 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1285 AN: 3468

East Asian (EAS) AF: 0.0247 AC: 128 AN: 5180

South Asian (SAS) AF: 0.256 AC: 1232 AN: 4816

European-Finnish (FIN) AF: 0.325 AC: 3435 AN: 10568

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.435 AC: 29596 AN: 67966

Other (OTH) AF: 0.423 AC: 894 AN: 2112

Alfa AF: 0.428 Hom.: 30844

Bravo AF: 0.440

Asia WGS AF: 0.173 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.33
PhyloP100		0.089
Mutation Taster		=100/0	polymorphism (auto)

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: rs845558; hg19: chr7-55247588;