rs712829

Variant names:

• chr7-55019062-G-T
• rs712829
• NM_005228.5:c.-216G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-55019062-G-T
• chr7-55019062-G-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.-216G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 265,078 control chromosomes in the GnomAD database, including 14,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6545 hom., cov: 33)
  • Exomes 𝑓: 0.35 (7521 hom.)
• Consequence: EGFR NM_005228.5 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.457
• Publications: 101 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: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• 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=-0.59).
• BP6: Variant 7-55019062-G-T is Benign according to our data. Variant chr7-55019062-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 1246877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 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.-216G>T		5_prime_UTR	Exon 1 of 28	NP_005219.2
	EGFR	NM_001346899.2		c.-216G>T		5_prime_UTR	Exon 1 of 27	NP_001333828.1
	EGFR	NM_001346898.2		c.-216G>T		5_prime_UTR	Exon 1 of 27	NP_001333827.1	E7BSV0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.-216G>T		5_prime_UTR	Exon 1 of 28	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.-216G>T		5_prime_UTR	Exon 1 of 26	ENSP00000415559.1	Q504U8
	EGFR	ENST00000344576.7	TSL:1	c.-216G>T		5_prime_UTR	Exon 1 of 16	ENSP00000345973.2	P00533-3

Frequencies

GnomAD3 genomes AF: 0.284 AC: 42919 AN: 150874 Hom.: 6550 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.348 AC: 39660 AN: 114100 Hom.: 7521 Cov.: 2 AF XY: 0.350 AC XY: 20618 AN XY: 58850

African (AFR) AF: 0.287 AC: 886 AN: 3086

American (AMR) AF: 0.270 AC: 841 AN: 3114

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 2172 AN: 4552

East Asian (EAS) AF: 0.0543 AC: 496 AN: 9132

South Asian (SAS) AF: 0.386 AC: 411 AN: 1064

European-Finnish (FIN) AF: 0.311 AC: 2852 AN: 9172

Middle Eastern (MID) AF: 0.534 AC: 331 AN: 620

European-Non Finnish (NFE) AF: 0.382 AC: 29001 AN: 75884

Other (OTH) AF: 0.357 AC: 2670 AN: 7476

GnomAD4 genome AF: 0.284 AC: 42904 AN: 150978 Hom.: 6545 Cov.: 33 AF XY: 0.280 AC XY: 20669 AN XY: 73738

African (AFR) AF: 0.235 AC: 9696 AN: 41332

American (AMR) AF: 0.266 AC: 4040 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1468 AN: 3462

East Asian (EAS) AF: 0.0475 AC: 241 AN: 5074

South Asian (SAS) AF: 0.299 AC: 1438 AN: 4810

European-Finnish (FIN) AF: 0.259 AC: 2647 AN: 10232

Middle Eastern (MID) AF: 0.459 AC: 134 AN: 292

European-Non Finnish (NFE) AF: 0.329 AC: 22223 AN: 67596

Other (OTH) AF: 0.345 AC: 722 AN: 2090

Alfa AF: 0.109 Hom.: 190

Bravo AF: 0.279

Asia WGS AF: 0.181 AC: 622 AN: 3422

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Lung cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.95
PhyloP100		-0.46
PromoterAI		0.21	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
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: rs712829; hg19: chr7-55086755; COSMIC: COSV51840530; COSMIC: COSV51840530;