rs773069229

Variant names:

• chr7-55019284-C-A
• rs773069229
• NM_005228.5:c.7C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55019284-C-A
• chr7-55019284-C-G
• chr7-55019284-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005228.5(EGFR):​c.7C>A​(p.Pro3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,352,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: EGFR NM_005228.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23613426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.7C>A	p.Pro3Thr	missense_variant	Exon 1 of 28	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.39e-7 AC: 1 AN: 1352994 Hom.: 0 Cov.: 30 AF XY: 0.00000149 AC XY: 1 AN XY: 670830

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000847 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;T;.;.;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.76	T;T;T;T;T;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.69	.;N;.;N;N;N
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.43	N;N;.;N;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.012	D;D;.;D;D;D
Sift4G	Benign	0.34	T;T;T;T;T;T
Polyphen		0.18	B;B;.;B;B;B
Vest4		0.23
MutPred		0.17		Gain of MoRF binding (P = 0.0775);Gain of MoRF binding (P = 0.0775);Gain of MoRF binding (P = 0.0775);Gain of MoRF binding (P = 0.0775);Gain of MoRF binding (P = 0.0775);Gain of MoRF binding (P = 0.0775);
MVP		0.70
MPC		0.60
ClinPred		0.081	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.042
gMVP		0.52

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: rs773069229; hg19: chr7-55086977;