rs17337135

chr7-55174889-G-Achr7-55174889-G-Cchr7-55174889-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005228.5(EGFR):c.2283+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,243,416 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (33 hom., cov: 33)
  • Exomes 𝑓: 0.023 (356 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.724

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=-0.79).
• BP6: Variant 7-55174889-G-A is Benign according to our data. Variant chr7-55174889-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1191430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2931/152286) while in subpopulation NFE AF= 0.0276 (1880/68030). AF 95% confidence interval is 0.0266. There are 33 homozygotes in gnomad4. There are 1311 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2283+69G>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2283+69G>A		intron_variant		1	NM_005228.5	P1
EGFR	ENST00000455089.5	c.2148+69G>A		intron_variant		1
EGFR	ENST00000450046.2	c.2124+69G>A		intron_variant		4
EGFR	ENST00000700145.1	c.632+69G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2935 AN: 152168 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.00990

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0383

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0254

GnomAD4 exome AF: 0.0227 AC: 24725 AN: 1091130 Hom.: 356 AF XY: 0.0227 AC XY: 12685 AN XY: 559150

Gnomad4 AFR exome AF: 0.00934

Gnomad4 AMR exome AF: 0.0157

Gnomad4 ASJ exome AF: 0.0334

Gnomad4 EAS exome AF: 0.0000264

Gnomad4 SAS exome AF: 0.0156

Gnomad4 FIN exome AF: 0.00885

Gnomad4 NFE exome AF: 0.0257

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0192 AC: 2931 AN: 152286 Hom.: 33 Cov.: 33 AF XY: 0.0176 AC XY: 1311 AN XY: 74450

Gnomad4 AFR AF: 0.00984

Gnomad4 AMR AF: 0.0182

Gnomad4 ASJ AF: 0.0383

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.00697

Gnomad4 NFE AF: 0.0276

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0279 Hom.: 12

Bravo AF: 0.0202

Asia WGS AF: 0.00925 AC: 32 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	3.9
Dann	Benign	0.63

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: rs17337135; hg19: chr7-55242582; COSMIC: COSV51791282; COSMIC: COSV51791282;