rs10228436

chr7-55170575-G-Achr7-55170575-G-Cchr7-55170575-G-T

Variant summary

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

The ENST00000344576.7(EGFR):c.*31G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,610,342 control chromosomes in the GnomAD database, including 100,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8535 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92134 hom.)
• Consequence: EGFR ENST00000344576.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.22

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=-0.97).
• BP6: Variant 7-55170575-G-A is Benign according to our data. Variant chr7-55170575-G-A is described in ClinVar as [Benign]. Clinvar id is 1289672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.1881-600G>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.1881-600G>A		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49272 AN: 151754 Hom.: 8538 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.358

GnomAD3 exomes AF: 0.371 AC: 92479 AN: 249574 Hom.: 17864 AF XY: 0.375 AC XY: 50635 AN XY: 135102

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.391

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.539

Gnomad SAS exome AF: 0.422

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.350 AC: 510302 AN: 1458470 Hom.: 92134 Cov.: 60 AF XY: 0.353 AC XY: 256083 AN XY: 725752

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.424

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.324 AC: 49277 AN: 151872 Hom.: 8535 Cov.: 32 AF XY: 0.329 AC XY: 24407 AN XY: 74234

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.359

Alfa AF: 0.352 Hom.: 17016

Bravo AF: 0.328

Asia WGS AF: 0.475 AC: 1649 AN: 3478

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 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.078
Dann	Benign	0.51

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: rs10228436; hg19: chr7-55238268; COSMIC: COSV51829087; COSMIC: COSV51829087;