rs2241055

Positions:

• chr7-55172768-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005228.5(EGFR):​c.1920-215G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 1,371,538 control chromosomes in the GnomAD database, including 79,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7786 hom., cov: 33)
  • Exomes 𝑓: 0.34 (71944 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP6: Variant 7-55172768-G-C is Benign according to our data. Variant chr7-55172768-G-C is described in ClinVar as [Benign]. Clinvar id is 1286588.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.1920-215G>C		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.1920-215G>C		intron_variant		1	NM_005228.5	P1
EGFR	ENST00000455089.5	c.1785-215G>C		intron_variant		1
EGFR	ENST00000450046.2	c.1761-215G>C		intron_variant		4
EGFR	ENST00000700145.1	c.269-215G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46673 AN: 152036 Hom.: 7783 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.337 AC: 411168 AN: 1219384 Hom.: 71944 AF XY: 0.339 AC XY: 206492 AN XY: 608784

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.594

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.307 AC: 46690 AN: 152154 Hom.: 7786 Cov.: 33 AF XY: 0.315 AC XY: 23402 AN XY: 74382

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.325

Alfa AF: 0.313 Hom.: 1003

Bravo AF: 0.300

Asia WGS AF: 0.451 AC: 1566 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-1.1
CADD	Benign	0.076
DANN	Benign	0.30

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: rs2241055; hg19: chr7-55240461; COSMIC: COSV99288772; COSMIC: COSV99288772;