7-55146750-G-A

Variant names:

• chr7-55146750-G-A
• rs7801956
• NM_005228.5:c.559+10G>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.559+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0865 in 1,613,864 control chromosomes in the GnomAD database, including 6,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (418 hom., cov: 33)
  • Exomes 𝑓: 0.089 (6200 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.81
• Publications: 22 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=-0.83).
• BP6: Variant 7-55146750-G-A is Benign according to our data. Variant chr7-55146750-G-A is described in ClinVar as Benign. ClinVar VariationId is 259681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0929 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.559+10G>A		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.424+3262G>A		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.400+10G>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.559+10G>A		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.424+3262G>A		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000344576.7	TSL:1	c.559+10G>A		intron	N/A	ENSP00000345973.2

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9829 AN: 152118 Hom.: 414 Cov.: 33

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.0974

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.0769

GnomAD2 exomes AF: 0.0762 AC: 19130 AN: 251086 AF XY: 0.0805

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.0412

Gnomad ASJ exome AF: 0.0950

Gnomad EAS exome AF: 0.0668

Gnomad FIN exome AF: 0.0492

Gnomad NFE exome AF: 0.0917

Gnomad OTH exome AF: 0.0837

GnomAD4 exome AF: 0.0888 AC: 129804 AN: 1461628 Hom.: 6200 Cov.: 36 AF XY: 0.0896 AC XY: 65123 AN XY: 727116

African (AFR) AF: 0.0163 AC: 545 AN: 33470

American (AMR) AF: 0.0436 AC: 1948 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0976 AC: 2551 AN: 26130

East Asian (EAS) AF: 0.0494 AC: 1961 AN: 39692

South Asian (SAS) AF: 0.106 AC: 9151 AN: 86238

European-Finnish (FIN) AF: 0.0528 AC: 2816 AN: 53374

Middle Eastern (MID) AF: 0.0704 AC: 406 AN: 5766

European-Non Finnish (NFE) AF: 0.0948 AC: 105423 AN: 1111864

Other (OTH) AF: 0.0829 AC: 5003 AN: 60386

GnomAD4 genome AF: 0.0647 AC: 9843 AN: 152236 Hom.: 418 Cov.: 33 AF XY: 0.0636 AC XY: 4737 AN XY: 74440

African (AFR) AF: 0.0205 AC: 853 AN: 41558

American (AMR) AF: 0.0593 AC: 908 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0974 AC: 338 AN: 3472

East Asian (EAS) AF: 0.0552 AC: 286 AN: 5182

South Asian (SAS) AF: 0.100 AC: 482 AN: 4806

European-Finnish (FIN) AF: 0.0510 AC: 540 AN: 10596

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0911 AC: 6197 AN: 67992

Other (OTH) AF: 0.0832 AC: 176 AN: 2116

Alfa AF: 0.0852 Hom.: 675

Bravo AF: 0.0632

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EGFR-related lung cancer Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Lung cancer Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.12
DANN	Benign	0.41
PhyloP100		-2.8
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: rs7801956; hg19: chr7-55214443; COSMIC: COSV51800215; COSMIC: COSV51800215;