rs9642391

Positions:

• chr7-55177671-G-C

Variant summary

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

The NM_005228.5(EGFR):​c.2283+2851G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,146 control chromosomes in the GnomAD database, including 5,992 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 (5992 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2283+2851G>C		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2283+2851G>C		intron_variant		1	NM_005228.5	P1
EGFR	ENST00000455089.5	c.2148+2851G>C		intron_variant		1
EGFR	ENST00000450046.2	c.2124+2851G>C		intron_variant		4
EGFR	ENST00000700145.1	c.632+2851G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38569 AN: 152028 Hom.: 5994 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.254 AC: 38569 AN: 152146 Hom.: 5992 Cov.: 32 AF XY: 0.263 AC XY: 19572 AN XY: 74380

Gnomad4 AFR AF: 0.0966

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.266

Alfa AF: 0.258 Hom.: 717

Bravo AF: 0.245

Asia WGS AF: 0.465 AC: 1614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.31
DANN	Benign	0.60

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: rs9642391; hg19: chr7-55245364;