7-55181233-T-C

Variant names:

• chr7-55181233-T-C
• rs10241451
• NM_005228.5:c.2284-60T>C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2284-60T>C		intron_variant	Intron 19 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2284-60T>C		intron_variant	Intron 19 of 27	1	NM_005228.5	ENSP00000275493.2

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

African (AFR) AF: 0.262 AC: 8617 AN: 32932

American (AMR) AF: 0.145 AC: 6467 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 7988 AN: 25976

East Asian (EAS) AF: 0.0580 AC: 2298 AN: 39592

South Asian (SAS) AF: 0.123 AC: 10546 AN: 85752

European-Finnish (FIN) AF: 0.193 AC: 10225 AN: 52980

Middle Eastern (MID) AF: 0.270 AC: 1306 AN: 4842

European-Non Finnish (NFE) AF: 0.210 AC: 229180 AN: 1091628

Other (OTH) AF: 0.211 AC: 12570 AN: 59532

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

African (AFR) AF: 0.260 AC: 10783 AN: 41538

American (AMR) AF: 0.180 AC: 2757 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 1036 AN: 3470

East Asian (EAS) AF: 0.0677 AC: 351 AN: 5182

South Asian (SAS) AF: 0.113 AC: 545 AN: 4824

European-Finnish (FIN) AF: 0.196 AC: 2079 AN: 10602

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14429 AN: 68008

Other (OTH) AF: 0.233 AC: 492 AN: 2114

Alfa AF: 0.223 Hom.: 516

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.68
PhyloP100		0.20
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: rs10241451; hg19: chr7-55248926; COSMIC: COSV51775300;