rs587777940

Variant names:

• chr7-55202667-T-A
• rs587777940
• ENST00000455089.5:c.3178T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55202667-T-A
• chr7-55202667-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001346898.2(EGFR):​c.3313T>A​(p.Ser1105Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1105A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFR NM_001346898.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06056729).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346898.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.3271+42T>A		intron	N/A	NP_005219.2
	EGFR	NM_001346898.2		c.3313T>A	p.Ser1105Thr	missense	Exon 27 of 27	NP_001333827.1
	EGFR	NM_001346897.2		c.3178T>A	p.Ser1060Thr	missense	Exon 26 of 26	NP_001333826.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000455089.5	TSL:1	c.3178T>A	p.Ser1060Thr	missense	Exon 26 of 26	ENSP00000415559.1
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.3271+42T>A		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000898199.1		c.3262+42T>A		intron	N/A	ENSP00000568258.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.31
DANN	Benign	0.15
DEOGEN2	Benign	0.22	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.1
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.066
Sift	Benign	0.55	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.18		Gain of glycosylation at S1059 (P = 0.0464)
MVP		0.52
ClinPred		0.019	T
GERP RS		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs587777940; hg19: chr7-55270360;