7-55181233-T-C

Position:

• chr7-55181233-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.2284-60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,590,172 control chromosomes in the GnomAD database, including 34,638 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3704 hom., cov: 34)
  • Exomes 𝑓: 0.20 (30934 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.199

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=-0.81).
• BP6: Variant 7-55181233-T-C is Benign according to our data. Variant chr7-55181233-T-C is described in ClinVar as [Benign]. Clinvar id is 1289881.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.2284-60T>C		intron_variant		ENST00000275493.7
EGFR-AS1	NR_047551.1	n.1338A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.2284-60T>C		intron_variant		1	NM_005228.5	P1
EGFR-AS1	ENST00000442411.2	n.1366A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32725 AN: 152132 Hom.: 3698 Cov.: 34

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.201 AC: 289197 AN: 1437922 Hom.: 30934 Cov.: 27 AF XY: 0.200 AC XY: 143119 AN XY: 716778

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.0580

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.215 AC: 32734 AN: 152250 Hom.: 3704 Cov.: 34 AF XY: 0.209 AC XY: 15579 AN XY: 74438

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.0677

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.233

Alfa AF: 0.221 Hom.: 489

Bravo AF: 0.218

Asia WGS AF: 0.102 AC: 355 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	-0.81
CADD	Benign	2.1
DANN	Benign	0.68

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: rs10241451; hg19: chr7-55248926; COSMIC: COSV51775300;