rs17335738

chr7-55019446-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005228.5(EGFR):c.88+81G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 918,674 control chromosomes in the GnomAD database, including 10,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1639 hom., cov: 33)
  • Exomes 𝑓: 0.15 (9058 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.295

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-55019446-G-T is Benign according to our data. Variant chr7-55019446-G-T is described in ClinVar as [Benign]. Clinvar id is 1263180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+81G>T		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+81G>T		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21778 AN: 150848 Hom.: 1635 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0321

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00217

Gnomad SAS AF: 0.0491

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0757

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.148 AC: 113646 AN: 767718 Hom.: 9058 AF XY: 0.149 AC XY: 55221 AN XY: 371462

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.245

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.000817

Gnomad4 SAS exome AF: 0.0613

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.144 AC: 21813 AN: 150956 Hom.: 1639 Cov.: 33 AF XY: 0.146 AC XY: 10738 AN XY: 73756

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.00218

Gnomad4 SAS AF: 0.0490

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.121

Alfa AF: 0.142 Hom.: 182

Bravo AF: 0.146

Asia WGS AF: 0.0500 AC: 173 AN: 3448

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	14
Dann	Benign	0.95

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: rs17335738; hg19: chr7-55087139;