7-55138237-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.89-4049A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,078 control chromosomes in the GnomAD database, including 8,303 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 0.31 (8303 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.89-4049A>T		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.89-4049A>T		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46967 AN: 151960 Hom.: 8316 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.309 AC: 46948 AN: 152078 Hom.: 8303 Cov.: 32 AF XY: 0.315 AC XY: 23402 AN XY: 74322

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.678

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.351

Gnomad4 OTH AF: 0.326

Alfa AF: 0.311 Hom.: 1071

Bravo AF: 0.304

Asia WGS AF: 0.464 AC: 1609 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.077
Dann	Benign	0.64

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: rs12666347; hg19: chr7-55205930;