rs2110290

Positions:

• chr7-55105075-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.89-37211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 152,114 control chromosomes in the GnomAD database, including 8,852 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 0.32 (8852 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.89-37211T>C		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.89-37211T>C		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49402 AN: 151996 Hom.: 8863 Cov.: 33

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.325 AC: 49396 AN: 152114 Hom.: 8852 Cov.: 33 AF XY: 0.335 AC XY: 24879 AN XY: 74354

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.297

Alfa AF: 0.324 Hom.: 16730

Bravo AF: 0.318

Asia WGS AF: 0.499 AC: 1734 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.73

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: rs2110290; hg19: chr7-55172768;