rs7799627

Positions:

• chr7-55093463-G-A
• chr7-55093463-G-C

Variant summary

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

The ENST00000275493.7(EGFR):​c.89-48823G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,112 control chromosomes in the GnomAD database, including 37,794 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 0.70 (37794 hom., cov: 32)
• Consequence: EGFR ENST00000275493.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-48823G>A		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.89-48823G>A		intron_variant		1	NM_005228.5	ENSP00000275493	P1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106585 AN: 151996 Hom.: 37743 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.970

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.701 AC: 106694 AN: 152112 Hom.: 37794 Cov.: 32 AF XY: 0.707 AC XY: 52560 AN XY: 74374

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.732

Alfa AF: 0.692 Hom.: 4592

Bravo AF: 0.704

Asia WGS AF: 0.877 AC: 3050 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	0.070
DANN	Benign	0.69

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: rs7799627; hg19: chr7-55161156;