rs845561

Variant names:

• chr7-55185015-C-T
• rs845561
• NM_005228.5:c.2469+3537C>T

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+3537C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,166 control chromosomes in the GnomAD database, including 44,093 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 0.75 (44093 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 17 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.2469+3537C>T		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.2334+3537C>T		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.2310+3537C>T		intron	N/A	NP_001333829.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2469+3537C>T		intron	N/A	ENSP00000275493.2
	EGFR	ENST00000455089.5	TSL:1	c.2334+3537C>T		intron	N/A	ENSP00000415559.1
	EGFR	ENST00000898199.1		c.2460+3537C>T		intron	N/A	ENSP00000568258.1

Frequencies

GnomAD3 genomes AF: 0.750 AC: 114091 AN: 152048 Hom.: 44046 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.759

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.751 AC: 114202 AN: 152166 Hom.: 44093 Cov.: 33 AF XY: 0.732 AC XY: 54471 AN XY: 74372

African (AFR) AF: 0.857 AC: 35603 AN: 41540

American (AMR) AF: 0.731 AC: 11173 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2853 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1260 AN: 5174

South Asian (SAS) AF: 0.533 AC: 2567 AN: 4816

European-Finnish (FIN) AF: 0.600 AC: 6341 AN: 10560

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51876 AN: 68000

Other (OTH) AF: 0.760 AC: 1603 AN: 2110

Alfa AF: 0.758 Hom.: 52423

Bravo AF: 0.766

Asia WGS AF: 0.469 AC: 1633 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.4
DANN	Benign	0.23
PhyloP100		-0.40
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: rs845561; hg19: chr7-55252708;