rs845562

chr7-55187112-A-Gchr7-55187112-A-T

Variant summary

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

The NM_005228.5(EGFR):c.2470-4607A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,182 control chromosomes in the GnomAD database, including 56,298 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 0.86 (56298 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338

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 = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2470-4607A>G		intron_variant		ENST00000275493.7
EGFR-AS1	NR_047551.1	n.93+1745T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2470-4607A>G		intron_variant		1	NM_005228.5	P1
EGFR-AS1	ENST00000442411.2	n.121+1745T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130364 AN: 152062 Hom.: 56242 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.898

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.858

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.857 AC: 130482 AN: 152182 Hom.: 56298 Cov.: 32 AF XY: 0.850 AC XY: 63228 AN XY: 74398

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.898

Gnomad4 EAS AF: 0.602

Gnomad4 SAS AF: 0.764

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.859

Alfa AF: 0.858 Hom.: 70747

Bravo AF: 0.866

Asia WGS AF: 0.749 AC: 2602 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	1.8
Dann	Benign	0.61

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: rs845562; hg19: chr7-55254805;