rs2017000

Positions:

• chr7-55174916-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005228.5(EGFR):​c.2283+96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 918,832 control chromosomes in the GnomAD database, including 47,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (6020 hom., cov: 33)
  • Exomes 𝑓: 0.32 (41644 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.389

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-55174916-A-G is Benign according to our data. Variant chr7-55174916-A-G is described in ClinVar as [Benign]. Clinvar id is 1238213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2283+96A>G		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2283+96A>G		intron_variant		1	NM_005228.5	ENSP00000275493	P1
EGFR	ENST00000455089.5	c.2148+96A>G		intron_variant		1		ENSP00000415559
EGFR	ENST00000450046.2	c.2124+96A>G		intron_variant		4		ENSP00000413354
EGFR	ENST00000700145.1	c.632+96A>G		intron_variant				ENSP00000514824

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38668 AN: 151958 Hom.: 6023 Cov.: 33

Gnomad AFR AF: 0.0968

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.616

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.317 AC: 242894 AN: 766756 Hom.: 41644 AF XY: 0.319 AC XY: 128980 AN XY: 404826

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.378

Gnomad4 EAS exome AF: 0.638

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.366

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.254 AC: 38667 AN: 152076 Hom.: 6020 Cov.: 33 AF XY: 0.264 AC XY: 19618 AN XY: 74344

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.616

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.268

Alfa AF: 0.278 Hom.: 7709

Bravo AF: 0.246

Asia WGS AF: 0.467 AC: 1623 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 07, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.17
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: rs2017000; hg19: chr7-55242609; COSMIC: COSV99288774; COSMIC: COSV99288774;