7-55182398-G-C

Variant names:

• chr7-55182398-G-C
• rs7795728
• NM_005228.5:c.2469+920G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.2469+920G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,116 control chromosomes in the GnomAD database, including 25,321 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.57 (25304 hom., cov: 32)
  • Exomes 𝑓: 0.61 (17 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155
• Publications: 8 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-AS1 (HGNC:40207): (EGFR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 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.2469+920G>C		intron	N/A	NP_005219.2
	EGFR-AS1	NR_047551.1		n.173C>G		non_coding_transcript_exon	Exon 2 of 2
	EGFR	NM_001346899.2		c.2334+920G>C		intron	N/A	NP_001333828.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2469+920G>C		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.2334+920G>C		intron	N/A	ENSP00000415559.1
	EGFR-AS1	ENST00000442411.3	TSL:2	n.210C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86485 AN: 151908 Hom.: 25281 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.611 AC: 55 AN: 90 Hom.: 17 Cov.: 0 AF XY: 0.577 AC XY: 45 AN XY: 78

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.671 AC: 47 AN: 70

Other (OTH) AF: 0.375 AC: 3 AN: 8

GnomAD4 genome AF: 0.569 AC: 86561 AN: 152026 Hom.: 25304 Cov.: 32 AF XY: 0.558 AC XY: 41426 AN XY: 74296

African (AFR) AF: 0.597 AC: 24739 AN: 41454

American (AMR) AF: 0.582 AC: 8899 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2315 AN: 3472

East Asian (EAS) AF: 0.175 AC: 904 AN: 5156

South Asian (SAS) AF: 0.485 AC: 2331 AN: 4808

European-Finnish (FIN) AF: 0.462 AC: 4869 AN: 10550

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40535 AN: 67996

Other (OTH) AF: 0.590 AC: 1244 AN: 2108

Alfa AF: 0.453 Hom.: 1175

Bravo AF: 0.581

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.37
PhyloP100		0.15
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7795728; hg19: chr7-55250091;