rs712830

Variant names:

• chr7-55019087-A-C
• rs712830
• NM_005228.5:c.-191A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-55019087-A-C
• chr7-55019087-A-G
• chr7-55019087-A-T

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.-191A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 305,792 control chromosomes in the GnomAD database, including 117,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60271 hom., cov: 33)
  • Exomes 𝑓: 0.86 (57599 hom.)
• Consequence: EGFR NM_005228.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.869
• Publications: 69 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

LOC105375284 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-55019087-A-C is Benign according to our data. Variant chr7-55019087-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1232163.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.-191A>C		5_prime_UTR_variant	Exon 1 of 28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.-191A>C		5_prime_UTR_variant	Exon 1 of 28	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.892 AC: 134487 AN: 150764 Hom.: 60232 Cov.: 33

Gnomad AFR AF: 0.973

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.907

GnomAD4 exome AF: 0.860 AC: 133275 AN: 154922 Hom.: 57599 Cov.: 3 AF XY: 0.860 AC XY: 69860 AN XY: 81212

African (AFR) AF: 0.968 AC: 3818 AN: 3944

American (AMR) AF: 0.794 AC: 3122 AN: 3934

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 5017 AN: 5578

East Asian (EAS) AF: 1.00 AC: 12504 AN: 12510

South Asian (SAS) AF: 0.938 AC: 2315 AN: 2468

European-Finnish (FIN) AF: 0.806 AC: 9659 AN: 11984

Middle Eastern (MID) AF: 0.938 AC: 747 AN: 796

European-Non Finnish (NFE) AF: 0.843 AC: 87806 AN: 104210

Other (OTH) AF: 0.872 AC: 8287 AN: 9498

GnomAD4 genome AF: 0.892 AC: 134576 AN: 150870 Hom.: 60271 Cov.: 33 AF XY: 0.890 AC XY: 65571 AN XY: 73662

African (AFR) AF: 0.973 AC: 40258 AN: 41386

American (AMR) AF: 0.825 AC: 12490 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.903 AC: 3129 AN: 3464

East Asian (EAS) AF: 0.998 AC: 5075 AN: 5086

South Asian (SAS) AF: 0.952 AC: 4595 AN: 4826

European-Finnish (FIN) AF: 0.824 AC: 8272 AN: 10042

Middle Eastern (MID) AF: 0.945 AC: 274 AN: 290

European-Non Finnish (NFE) AF: 0.854 AC: 57716 AN: 67618

Other (OTH) AF: 0.905 AC: 1901 AN: 2100

Alfa AF: 0.874 Hom.: 7232

Bravo AF: 0.895

Asia WGS AF: 0.949 AC: 3123 AN: 3292

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lung cancer Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Likely 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	-0.87
CADD	Benign	8.7
DANN	Benign	0.38
PhyloP100		-0.87
PromoterAI		0.0041	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs712830; hg19: chr7-55086780;