chr7-55170771-T-G

Variant names:

• chr7-55170771-T-G
• rs10277413
• ENST00000344576.7:c.*227T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000344576.7(EGFR):​c.*227T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,442,118 control chromosomes in the GnomAD database, including 89,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8660 hom., cov: 32)
  • Exomes 𝑓: 0.35 (80626 hom.)
• Consequence: EGFR ENST00000344576.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.577
• Publications: 20 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 Gene-Disease associations (from GenCC):

• lung cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
• non-small cell lung carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• inflammatory skin and bowel disease, neonatal, 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neonatal inflammatory skin and bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-55170771-T-G is Benign according to our data. Variant chr7-55170771-T-G is described in ClinVar as Benign. ClinVar VariationId is 1274013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1881-404T>G		intron_variant	Intron 15 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.1881-404T>G		intron_variant	Intron 15 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49643 AN: 151958 Hom.: 8663 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.348 AC: 449012 AN: 1290044 Hom.: 80626 Cov.: 35 AF XY: 0.351 AC XY: 219938 AN XY: 627260

African (AFR) AF: 0.224 AC: 6437 AN: 28692

American (AMR) AF: 0.366 AC: 8295 AN: 22644

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 9318 AN: 19124

East Asian (EAS) AF: 0.607 AC: 20941 AN: 34488

South Asian (SAS) AF: 0.424 AC: 26887 AN: 63484

European-Finnish (FIN) AF: 0.327 AC: 9734 AN: 29746

Middle Eastern (MID) AF: 0.452 AC: 1618 AN: 3576

European-Non Finnish (NFE) AF: 0.334 AC: 345779 AN: 1034870

Other (OTH) AF: 0.374 AC: 20003 AN: 53420

GnomAD4 genome AF: 0.326 AC: 49648 AN: 152074 Hom.: 8660 Cov.: 32 AF XY: 0.331 AC XY: 24632 AN XY: 74342

African (AFR) AF: 0.232 AC: 9617 AN: 41492

American (AMR) AF: 0.362 AC: 5522 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1656 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2858 AN: 5168

South Asian (SAS) AF: 0.439 AC: 2114 AN: 4818

European-Finnish (FIN) AF: 0.331 AC: 3498 AN: 10566

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23183 AN: 67984

Other (OTH) AF: 0.357 AC: 755 AN: 2112

Alfa AF: 0.334 Hom.: 10666

Bravo AF: 0.329

Asia WGS AF: 0.475 AC: 1652 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	-0.91
CADD	Benign	0.59
DANN	Benign	0.19
PhyloP100		-0.58
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: rs10277413; hg19: chr7-55238464; COSMIC: COSV99288767;