rs17172433

Positions:

• chr7-55074742-G-A

Variant summary

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

The NM_005228.5(EGFR):​c.88+55377G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,124 control chromosomes in the GnomAD database, including 2,131 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 0.16 (2131 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.160

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+55377G>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+55377G>A		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23738 AN: 152006 Hom.: 2132 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.156 AC: 23741 AN: 152124 Hom.: 2131 Cov.: 33 AF XY: 0.154 AC XY: 11448 AN XY: 74374

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0646

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0495

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.122

Alfa AF: 0.127 Hom.: 1086

Bravo AF: 0.157

Asia WGS AF: 0.0440 AC: 152 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.8
DANN	Benign	0.48

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: rs17172433; hg19: chr7-55142435;