rs11506105

chr7-55152484-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005228.5(EGFR):c.629-62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,463,048 control chromosomes in the GnomAD database, including 246,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26081 hom., cov: 32)
  • Exomes 𝑓: 0.58 (220309 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.19

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-55152484-A-G is Benign according to our data. Variant chr7-55152484-A-G is described in ClinVar as [Benign]. Clinvar id is 1277571.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.629-62A>G		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.629-62A>G		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88559 AN: 151928 Hom.: 26040 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 0.577 AC: 756264 AN: 1311002 Hom.: 220309 Cov.: 20 AF XY: 0.577 AC XY: 381421 AN XY: 660530

Gnomad4 AFR exome AF: 0.651

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.602

Gnomad4 FIN exome AF: 0.539

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.582

GnomAD4 genome AF: 0.583 AC: 88667 AN: 152046 Hom.: 26081 Cov.: 32 AF XY: 0.576 AC XY: 42821 AN XY: 74328

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.529

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.584

Alfa AF: 0.579 Hom.: 29764

Bravo AF: 0.587

Asia WGS AF: 0.501 AC: 1746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 29, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.012
Dann	Benign	0.49

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: rs11506105; hg19: chr7-55220177; COSMIC: COSV51766104;