rs1554718

Positions:

• chr7-55188270-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2470-3449T>C		intron_variant		ENST00000275493.7	NP_005219.2
EGFR-AS1	NR_047551.1	n.93+587A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2470-3449T>C		intron_variant		1	NM_005228.5	ENSP00000275493	P1
EGFR-AS1	ENST00000442411.2	n.121+587A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.538

Alfa AF: 0.583 Hom.: 34388

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554718; hg19: chr7-55255963;