chr7-55192255-C-G

Position:

• chr7-55192255-C-G

Variant summary

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

The NM_005228.5(EGFR):​c.2625+381C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,094 control chromosomes in the GnomAD database, including 5,934 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 0.25 (5934 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2625+381C>G		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2625+381C>G		intron_variant		1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000455089.5	c.2490+381C>G		intron_variant		1		ENSP00000415559.1
EGFR	ENST00000450046.2	c.2466+381C>G		intron_variant		4		ENSP00000413354.2
EGFR	ENST00000700145.1	c.897+456C>G		intron_variant				ENSP00000514824.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37464 AN: 151974 Hom.: 5939 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.246 AC: 37466 AN: 152094 Hom.: 5934 Cov.: 32 AF XY: 0.265 AC XY: 19718 AN XY: 74344

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.231

Alfa AF: 0.130 Hom.: 224

Bravo AF: 0.230

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.50

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: rs17337331; hg19: chr7-55259948;