rs13222385

chr7-55183900-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
EGFR	NM_005228.5	c.2469+2422A>G		intron_variant		ENST00000275493.7
EGFR-AS1	NR_047551.1	n.94-1423T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2469+2422A>G		intron_variant		1	NM_005228.5	P1
EGFR-AS1	ENST00000442411.2	n.122-1423T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.313

Alfa AF: 0.370 Hom.: 14182

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

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: rs13222385; hg19: chr7-55251593; COSMIC: COSV51774007;