rs1015793

Variant names:

• chr7-55046623-A-G
• rs1015793
• NM_005228.5:c.88+27258A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-55046623-A-G
• chr7-55046623-A-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.88+27258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 151,888 control chromosomes in the GnomAD database, including 3,156 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 0.19 (3156 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.88+27258A>G		intron_variant	Intron 1 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.88+27258A>G		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28361 AN: 151778 Hom.: 3155 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.0440

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.187 AC: 28384 AN: 151888 Hom.: 3156 Cov.: 32 AF XY: 0.185 AC XY: 13721 AN XY: 74220

Gnomad4 AFR AF: 0.305 AC: 0.305376 AN: 0.305376

Gnomad4 AMR AF: 0.153 AC: 0.153111 AN: 0.153111

Gnomad4 ASJ AF: 0.0982 AC: 0.0982143 AN: 0.0982143

Gnomad4 EAS AF: 0.0441 AC: 0.0441347 AN: 0.0441347

Gnomad4 SAS AF: 0.0789 AC: 0.0789364 AN: 0.0789364

Gnomad4 FIN AF: 0.187 AC: 0.186617 AN: 0.186617

Gnomad4 NFE AF: 0.147 AC: 0.146984 AN: 0.146984

Gnomad4 OTH AF: 0.156 AC: 0.155955 AN: 0.155955

Alfa AF: 0.149 Hom.: 3663

Bravo AF: 0.190

Asia WGS AF: 0.118 AC: 409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.29
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

Publications

LitVar

Other links and lift over

dbSNP: rs1015793; hg19: chr7-55114316;