rs7796872

Positions:

• chr7-55112151-G-A
• chr7-55112151-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.89-30135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,294 control chromosomes in the GnomAD database, including 1,133 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 0.10 (1133 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-30135G>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.89-30135G>A		intron_variant		1	NM_005228.5	ENSP00000275493	P1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15330 AN: 152176 Hom.: 1125 Cov.: 33

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.0996

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

GnomAD4 genome AF: 0.101 AC: 15352 AN: 152294 Hom.: 1133 Cov.: 33 AF XY: 0.101 AC XY: 7499 AN XY: 74476

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0820

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.0986

Alfa AF: 0.118 Hom.: 1411

Bravo AF: 0.104

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.77

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: rs7796872; hg19: chr7-55179844;