7-55174062-G-A

Variant names:

• chr7-55174062-G-A
• rs17337107
• NM_005228.5:c.2184+19G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005228.5(EGFR):​c.2184+19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 1,614,116 control chromosomes in the GnomAD database, including 1,835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (107 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1728 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.42
• Publications: 16 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 Gene-Disease associations (from GenCC):

• lung cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
• non-small cell lung carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• inflammatory skin and bowel disease, neonatal, 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neonatal inflammatory skin and bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 7-55174062-G-A is Benign according to our data. Variant chr7-55174062-G-A is described in ClinVar as Benign. ClinVar VariationId is 1251320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0528 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.2184+19G>A		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.2049+19G>A		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.2025+19G>A		intron	N/A	NP_001333829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2184+19G>A		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.2049+19G>A		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000898199.1		c.2175+19G>A		intron	N/A	ENSP00000568258.1

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4599 AN: 152242 Hom.: 105 Cov.: 33

Gnomad AFR AF: 0.00909

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0582

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0463

Gnomad OTH AF: 0.0310

GnomAD2 exomes AF: 0.0361 AC: 9054 AN: 250792 AF XY: 0.0394

Gnomad AFR exome AF: 0.00681

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0378

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0236

Gnomad NFE exome AF: 0.0462

Gnomad OTH exome AF: 0.0381

GnomAD4 exome AF: 0.0454 AC: 66374 AN: 1461756 Hom.: 1728 Cov.: 32 AF XY: 0.0464 AC XY: 33754 AN XY: 727170

African (AFR) AF: 0.00654 AC: 219 AN: 33478

American (AMR) AF: 0.0155 AC: 692 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 1062 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0694 AC: 5988 AN: 86252

European-Finnish (FIN) AF: 0.0255 AC: 1363 AN: 53358

Middle Eastern (MID) AF: 0.0403 AC: 232 AN: 5754

European-Non Finnish (NFE) AF: 0.0489 AC: 54357 AN: 1111968

Other (OTH) AF: 0.0407 AC: 2459 AN: 60392

GnomAD4 genome AF: 0.0302 AC: 4601 AN: 152360 Hom.: 107 Cov.: 33 AF XY: 0.0299 AC XY: 2231 AN XY: 74516

African (AFR) AF: 0.00906 AC: 377 AN: 41600

American (AMR) AF: 0.0182 AC: 278 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0584 AC: 282 AN: 4826

European-Finnish (FIN) AF: 0.0251 AC: 267 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0463 AC: 3148 AN: 68024

Other (OTH) AF: 0.0307 AC: 65 AN: 2116

Alfa AF: 0.0376 Hom.: 39

Bravo AF: 0.0278

Asia WGS AF: 0.0250 AC: 88 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	EGFR-related lung cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.58
DANN	Benign	0.72
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs17337107; hg19: chr7-55241755; COSMIC: COSV51810588;