chr7-55183101-C-T

Variant names:

• chr7-55183101-C-T
• rs845560
• NM_005228.5:c.2469+1623C>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+1623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,046 control chromosomes in the GnomAD database, including 4,712 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 0.23 (4712 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 11 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 (EAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2469+1623C>T		intron_variant	Intron 20 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2469+1623C>T		intron_variant	Intron 20 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35497 AN: 151928 Hom.: 4711 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.234 AC: 35503 AN: 152046 Hom.: 4712 Cov.: 32 AF XY: 0.238 AC XY: 17706 AN XY: 74292

African (AFR) AF: 0.124 AC: 5159 AN: 41496

American (AMR) AF: 0.259 AC: 3969 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 789 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2152 AN: 5140

South Asian (SAS) AF: 0.279 AC: 1340 AN: 4802

European-Finnish (FIN) AF: 0.340 AC: 3590 AN: 10562

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17725 AN: 67964

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.213 Hom.: 1671

Bravo AF: 0.224

Asia WGS AF: 0.343 AC: 1191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.49
PhyloP100		-1.7
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: rs845560; hg19: chr7-55250794;