rs845558

chr7-55179895-G-Achr7-55179895-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2284-1398G>A		intron_variant		ENST00000275493.7
EGFR-AS1	NR_047551.1	n.2676C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2284-1398G>A		intron_variant		1	NM_005228.5	P1
EGFR-AS1	ENST00000442411.2	n.2704C>T		non_coding_transcript_exon_variant	2/2	2

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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.423

Alfa AF: 0.428 Hom.: 20528

Bravo AF: 0.440

Asia WGS AF: 0.173 AC: 606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs845558; hg19: chr7-55247588; COSMIC: COSV51773998;