7-55197661-A-T

Position:

• chr7-55197661-A-T

Variant summary

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

The NM_005228.5(EGFR):​c.2702-1056A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 152,144 control chromosomes in the GnomAD database, including 40,419 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 0.73 (40419 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.631

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2702-1056A>T		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2702-1056A>T		intron_variant		1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.727 AC: 110447 AN: 152026 Hom.: 40377 Cov.: 33

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.727 AC: 110546 AN: 152144 Hom.: 40419 Cov.: 33 AF XY: 0.723 AC XY: 53773 AN XY: 74368

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.777

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.644

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.750

Alfa AF: 0.642 Hom.: 2012

Bravo AF: 0.739

Asia WGS AF: 0.632 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.67

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: rs2740763; hg19: chr7-55265354;