chr7-55199064-C-T

Variant names:

• chr7-55199064-C-T
• rs2293348
• NM_005228.5:c.2848+201C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005228.5(EGFR):​c.2848+201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,192 control chromosomes in the GnomAD database, including 5,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (5626 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.558
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-55199064-C-T is Benign according to our data. Variant chr7-55199064-C-T is described in ClinVar as Benign. ClinVar VariationId is 1227710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.2848+201C>T		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.2713+201C>T		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.2689+201C>T		intron	N/A	NP_001333829.1	C9JYS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2848+201C>T		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.2713+201C>T		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000898199.1		c.2839+201C>T		intron	N/A	ENSP00000568258.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39131 AN: 152074 Hom.: 5615 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.288

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.257 AC: 39159 AN: 152192 Hom.: 5626 Cov.: 33 AF XY: 0.254 AC XY: 18894 AN XY: 74398

African (AFR) AF: 0.142 AC: 5881 AN: 41538

American (AMR) AF: 0.366 AC: 5594 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1197 AN: 3472

East Asian (EAS) AF: 0.126 AC: 653 AN: 5186

South Asian (SAS) AF: 0.290 AC: 1396 AN: 4822

European-Finnish (FIN) AF: 0.199 AC: 2103 AN: 10584

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21400 AN: 67980

Other (OTH) AF: 0.292 AC: 617 AN: 2114

Alfa AF: 0.299 Hom.: 14379

Bravo AF: 0.264

Asia WGS AF: 0.235 AC: 819 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.59
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2293348; hg19: chr7-55266757;