7-55182398-G-C

Position:

• chr7-55182398-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+920G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,116 control chromosomes in the GnomAD database, including 25,321 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 0.57 (25304 hom., cov: 32)
  • Exomes 𝑓: 0.61 (17 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2469+920G>C		intron_variant		ENST00000275493.7	NP_005219.2
EGFR-AS1	NR_047551.1	n.173C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2469+920G>C		intron_variant		1	NM_005228.5	ENSP00000275493	P1
EGFR-AS1	ENST00000442411.2	n.201C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86485 AN: 151908 Hom.: 25281 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.579

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.611 AC: 55 AN: 90 Hom.: 17 Cov.: 0 AF XY: 0.577 AC XY: 45 AN XY: 78

Gnomad4 AFR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.671

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.569 AC: 86561 AN: 152026 Hom.: 25304 Cov.: 32 AF XY: 0.558 AC XY: 41426 AN XY: 74296

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.582

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.590

Alfa AF: 0.453 Hom.: 1175

Bravo AF: 0.581

Asia WGS AF: 0.389 AC: 1353 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	1.3
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7795728; hg19: chr7-55250091;