rs6593210

chr7-55186493-G-Achr7-55186493-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):c.2469+5015G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,144 control chromosomes in the GnomAD database, including 3,018 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 (3018 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0610

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2469+5015G>A		intron_variant		ENST00000275493.7
EGFR-AS1	NR_047551.1	n.93+2364C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2469+5015G>A		intron_variant		1	NM_005228.5	P1
EGFR-AS1	ENST00000442411.2	n.121+2364C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29583 AN: 152026 Hom.: 3014 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.194 AC: 29586 AN: 152144 Hom.: 3018 Cov.: 33 AF XY: 0.190 AC XY: 14142 AN XY: 74364

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.0666

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.216

Alfa AF: 0.209 Hom.: 4789

Bravo AF: 0.194

Asia WGS AF: 0.0950 AC: 330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.1
Dann	Benign	0.75

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: rs6593210; hg19: chr7-55254186;