7-55037627-A-G

Variant names:

• chr7-55037627-A-G
• rs12718939
• NM_005228.5:c.88+18262A>G

Variant summary

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

The NM_005228.5(EGFR):​c.88+18262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,072 control chromosomes in the GnomAD database, including 42,986 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 0.75 (42986 hom., cov: 31)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.784

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+18262A>G		intron_variant	Intron 1 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.88+18262A>G		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113740 AN: 151952 Hom.: 42918 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.749 AC: 113875 AN: 152072 Hom.: 42986 Cov.: 31 AF XY: 0.754 AC XY: 56033 AN XY: 74332

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.795

Gnomad4 ASJ AF: 0.718

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.768

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.741

Alfa AF: 0.702 Hom.: 26708

Bravo AF: 0.757

Asia WGS AF: 0.843 AC: 2932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.79
DANN	Benign	0.30

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: rs12718939; hg19: chr7-55105320;