rs6964705

Positions:

• chr7-55141944-C-A
• chr7-55141944-C-G
• chr7-55141944-C-T

Variant summary

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

The ENST00000275493.7(EGFR):​c.89-342C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 152,096 control chromosomes in the GnomAD database, including 14,016 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 0.41 (14016 hom., cov: 33)
• Consequence: EGFR ENST00000275493.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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 = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-342C>A		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.89-342C>A		intron_variant		1	NM_005228.5	ENSP00000275493	P1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63011 AN: 151980 Hom.: 14033 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.409

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.422

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

GnomAD4 genome AF: 0.414 AC: 62999 AN: 152096 Hom.: 14016 Cov.: 33 AF XY: 0.422 AC XY: 31382 AN XY: 74336

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.528

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.419

Alfa AF: 0.449 Hom.: 24109

Bravo AF: 0.401

Asia WGS AF: 0.487 AC: 1690 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	0.98
DANN	Benign	0.19

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: rs6964705; hg19: chr7-55209637;