7-55181094-T-C

Position:

• chr7-55181094-T-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.2284-199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 666,234 control chromosomes in the GnomAD database, including 108,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25517 hom., cov: 33)
  • Exomes 𝑓: 0.56 (82875 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.40

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]

EGFR-AS1 (HGNC:40207): (EGFR antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-55181094-T-C is Benign according to our data. Variant chr7-55181094-T-C is described in ClinVar as [Benign]. Clinvar id is 1276464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2284-199T>C		intron_variant		ENST00000275493.7
EGFR-AS1	NR_047551.1	n.1477A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2284-199T>C		intron_variant		1	NM_005228.5	P1
EGFR-AS1	ENST00000442411.2	n.1505A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86863 AN: 152012 Hom.: 25493 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.555 AC: 285506 AN: 514102 Hom.: 82875 Cov.: 6 AF XY: 0.555 AC XY: 149832 AN XY: 270042

Gnomad4 AFR exome AF: 0.601

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.471

Gnomad4 NFE exome AF: 0.599

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.571 AC: 86941 AN: 152132 Hom.: 25517 Cov.: 33 AF XY: 0.560 AC XY: 41620 AN XY: 74380

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.591

Alfa AF: 0.595 Hom.: 5450

Bravo AF: 0.584

Asia WGS AF: 0.397 AC: 1381 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	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.042
DANN	Benign	0.31

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: rs10241326; hg19: chr7-55248787;