rs1554718

Variant names:

• chr7-55188270-T-C
• rs1554718
• NM_005228.5:c.2470-3449T>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.2470-3449T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 151,840 control chromosomes in the GnomAD database, including 19,873 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 0.50 (19873 hom., cov: 31)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• 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-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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2470-3449T>C		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.2470-3449T>C		intron_variant	Intron 20 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75212 AN: 151722 Hom.: 19855 Cov.: 31

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.496 AC: 75256 AN: 151840 Hom.: 19873 Cov.: 31 AF XY: 0.488 AC XY: 36180 AN XY: 74202

African (AFR) AF: 0.345 AC: 14264 AN: 41386

American (AMR) AF: 0.547 AC: 8351 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2264 AN: 3468

East Asian (EAS) AF: 0.195 AC: 1004 AN: 5138

South Asian (SAS) AF: 0.480 AC: 2303 AN: 4798

European-Finnish (FIN) AF: 0.461 AC: 4862 AN: 10544

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40365 AN: 67930

Other (OTH) AF: 0.538 AC: 1132 AN: 2106

Alfa AF: 0.575 Hom.: 42386

Bravo AF: 0.495

Asia WGS AF: 0.369 AC: 1283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.10
DANN	Benign	0.17
PhyloP100		-3.0
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: rs1554718; hg19: chr7-55255963;