rs13222385

Variant names:

• chr7-55183900-A-G
• rs13222385
• NM_005228.5:c.2469+2422A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.2469+2422A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 151,960 control chromosomes in the GnomAD database, including 7,522 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 0.29 (7522 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.674
• Publications: 18 publications found

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-AS1 (HGNC:40207): (EGFR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2469+2422A>G		intron_variant	Intron 20 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2469+2422A>G		intron_variant	Intron 20 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43442 AN: 151842 Hom.: 7507 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.286 AC: 43481 AN: 151960 Hom.: 7522 Cov.: 33 AF XY: 0.283 AC XY: 20987 AN XY: 74278

African (AFR) AF: 0.103 AC: 4262 AN: 41444

American (AMR) AF: 0.374 AC: 5719 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3468

East Asian (EAS) AF: 0.110 AC: 567 AN: 5174

South Asian (SAS) AF: 0.368 AC: 1768 AN: 4804

European-Finnish (FIN) AF: 0.266 AC: 2809 AN: 10550

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25970 AN: 67938

Other (OTH) AF: 0.313 AC: 659 AN: 2106

Alfa AF: 0.361 Hom.: 17388

Bravo AF: 0.284

Asia WGS AF: 0.267 AC: 929 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	0.075
DANN	Benign	0.52
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13222385; hg19: chr7-55251593;