rs759160

Positions:

• chr7-55113749-G-A
• chr7-55113749-G-C
• chr7-55113749-G-T

Variant summary

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

The NM_005228.5(EGFR):​c.89-28537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,182 control chromosomes in the GnomAD database, including 41,540 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 0.73 (41540 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.89-28537G>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.89-28537G>A		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111640 AN: 152064 Hom.: 41516 Cov.: 33

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.734 AC: 111716 AN: 152182 Hom.: 41540 Cov.: 33 AF XY: 0.736 AC XY: 54772 AN XY: 74400

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.760

Alfa AF: 0.755 Hom.: 57006

Bravo AF: 0.735

Asia WGS AF: 0.926 AC: 3220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.023
DANN	Benign	0.26

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: rs759160; hg19: chr7-55181442;