NM_005228.5:c.*774T>C

Variant names:

• chr7-55206391-T-C
• rs884225
• NM_005228.5:c.*774T>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.*774T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 233,320 control chromosomes in the GnomAD database, including 2,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1226 hom., cov: 32)
  • Exomes 𝑓: 0.14 (1256 hom.)
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960
• Publications: 33 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 7-55206391-T-C is Benign according to our data. Variant chr7-55206391-T-C is described in ClinVar as Benign. ClinVar VariationId is 1253347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 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.*774T>C		3_prime_UTR	Exon 28 of 28	NP_005219.2
	EGFR	NM_001346899.2		c.*774T>C		3_prime_UTR	Exon 27 of 27	NP_001333828.1
	EGFR	NM_001346900.2		c.*774T>C		3_prime_UTR	Exon 28 of 28	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.*774T>C		3_prime_UTR	Exon 28 of 28	ENSP00000275493.2	P00533-1
	EGFR	ENST00000450046.2	TSL:4	c.*774T>C		3_prime_UTR	Exon 28 of 28	ENSP00000413354.2	C9JYS6
	EGFR	ENST00000700146.1		n.2151T>C		non_coding_transcript_exon	Exon 6 of 6

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15265 AN: 152116 Hom.: 1228 Cov.: 32

Gnomad AFR AF: 0.0635

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.0809

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0897

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.139 AC: 11289 AN: 81086 Hom.: 1256 Cov.: 0 AF XY: 0.137 AC XY: 5097 AN XY: 37272

African (AFR) AF: 0.0670 AC: 261 AN: 3896

American (AMR) AF: 0.107 AC: 268 AN: 2504

Ashkenazi Jewish (ASJ) AF: 0.0814 AC: 417 AN: 5124

East Asian (EAS) AF: 0.411 AC: 4686 AN: 11406

South Asian (SAS) AF: 0.214 AC: 150 AN: 700

European-Finnish (FIN) AF: 0.0833 AC: 6 AN: 72

Middle Eastern (MID) AF: 0.134 AC: 66 AN: 492

European-Non Finnish (NFE) AF: 0.0932 AC: 4673 AN: 50118

Other (OTH) AF: 0.112 AC: 762 AN: 6774

GnomAD4 genome AF: 0.100 AC: 15266 AN: 152234 Hom.: 1226 Cov.: 32 AF XY: 0.104 AC XY: 7743 AN XY: 74438

African (AFR) AF: 0.0635 AC: 2638 AN: 41550

American (AMR) AF: 0.0983 AC: 1503 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0809 AC: 281 AN: 3472

East Asian (EAS) AF: 0.461 AC: 2383 AN: 5166

South Asian (SAS) AF: 0.201 AC: 968 AN: 4820

European-Finnish (FIN) AF: 0.0965 AC: 1023 AN: 10606

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0897 AC: 6100 AN: 68016

Other (OTH) AF: 0.112 AC: 237 AN: 2110

Alfa AF: 0.0903 Hom.: 662

Bravo AF: 0.103

Asia WGS AF: 0.266 AC: 928 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		0.096
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs884225; hg19: chr7-55274084;