7-55086943-T-C

Position:

• chr7-55086943-T-C

Variant summary

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

The NM_005228.5(EGFR):​c.89-55343T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,166 control chromosomes in the GnomAD database, including 59,752 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 0.88 (59752 hom., cov: 31)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-55343T>C		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.89-55343T>C		intron_variant		1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134539 AN: 152048 Hom.: 59697 Cov.: 31

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.889

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.885 AC: 134652 AN: 152166 Hom.: 59752 Cov.: 31 AF XY: 0.888 AC XY: 66083 AN XY: 74400

Gnomad4 AFR AF: 0.939

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.839

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.882

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.874

Alfa AF: 0.852 Hom.: 73642

Bravo AF: 0.889

Asia WGS AF: 0.929 AC: 3229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.65

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: rs759169; hg19: chr7-55154636;