7-55160480-C-T

Position:

• chr7-55160480-C-T

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.1498+142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 903,888 control chromosomes in the GnomAD database, including 255,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41496 hom., cov: 34)
  • Exomes 𝑓: 0.75 (214126 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.564

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=-0.91).
• BP6: Variant 7-55160480-C-T is Benign according to our data. Variant chr7-55160480-C-T is described in ClinVar as [Benign]. Clinvar id is 1274112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1498+142C>T		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.1498+142C>T		intron_variant		1	NM_005228.5	ENSP00000275493	P1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111754 AN: 152084 Hom.: 41462 Cov.: 34

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.831

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.750 AC: 563526 AN: 751686 Hom.: 214126 AF XY: 0.755 AC XY: 289965 AN XY: 384106

Gnomad4 AFR exome AF: 0.661

Gnomad4 AMR exome AF: 0.841

Gnomad4 ASJ exome AF: 0.788

Gnomad4 EAS exome AF: 0.998

Gnomad4 SAS exome AF: 0.878

Gnomad4 FIN exome AF: 0.710

Gnomad4 NFE exome AF: 0.721

Gnomad4 OTH exome AF: 0.761

GnomAD4 genome AF: 0.735 AC: 111844 AN: 152202 Hom.: 41496 Cov.: 34 AF XY: 0.742 AC XY: 55194 AN XY: 74412

Gnomad4 AFR AF: 0.667

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.756

Alfa AF: 0.736 Hom.: 21101

Bravo AF: 0.740

Asia WGS AF: 0.928 AC: 3230 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	Jan 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.41

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: rs759162; hg19: chr7-55228173;