7-55209694-C-T

Variant names:

• chr7-55209694-C-T
• rs940810
• NM_005228.5:c.*4077C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.*4077C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,236 control chromosomes in the GnomAD database, including 3,713 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3713 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.*4077C>T		3_prime_UTR_variant	Exon 28 of 28	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.*4077C>T		3_prime_UTR_variant	Exon 28 of 28	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000450046.2	c.*4077C>T		3_prime_UTR_variant	Exon 28 of 28	4		ENSP00000413354.2
EGFR-AS1	ENST00000836806.1	n.207+3069G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30050 AN: 152110 Hom.: 3704 Cov.: 32

Gnomad AFR AF: 0.0642

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.0679

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.250 AC: 2 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.333 AC: 2 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.197 AC: 30064 AN: 152228 Hom.: 3713 Cov.: 32 AF XY: 0.196 AC XY: 14604 AN XY: 74432

African (AFR) AF: 0.0640 AC: 2659 AN: 41558

American (AMR) AF: 0.322 AC: 4920 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1023 AN: 3466

East Asian (EAS) AF: 0.0678 AC: 352 AN: 5188

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4812

European-Finnish (FIN) AF: 0.157 AC: 1670 AN: 10608

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17453 AN: 67986

Other (OTH) AF: 0.227 AC: 479 AN: 2110

Alfa AF: 0.237 Hom.: 8875

Bravo AF: 0.203

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		-0.54
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: rs940810; hg19: chr7-55277387;