7-55194934-T-C

Variant names:

• chr7-55194934-T-C
• rs1404908
• NM_005228.5:c.2701+2093T>C

Variant summary

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

The NM_005228.5(EGFR):​c.2701+2093T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,028 control chromosomes in the GnomAD database, including 30,821 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 0.63 (30821 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.874 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2701+2093T>C		intron_variant	Intron 22 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2701+2093T>C		intron_variant	Intron 22 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95318 AN: 151910 Hom.: 30792 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.613

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.627 AC: 95394 AN: 152028 Hom.: 30821 Cov.: 32 AF XY: 0.639 AC XY: 47539 AN XY: 74338

African (AFR) AF: 0.498 AC: 20640 AN: 41436

American (AMR) AF: 0.687 AC: 10496 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2088 AN: 3470

East Asian (EAS) AF: 0.896 AC: 4638 AN: 5178

South Asian (SAS) AF: 0.818 AC: 3940 AN: 4814

European-Finnish (FIN) AF: 0.711 AC: 7525 AN: 10584

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44015 AN: 67946

Other (OTH) AF: 0.616 AC: 1300 AN: 2112

Alfa AF: 0.607 Hom.: 8327

Bravo AF: 0.618

Asia WGS AF: 0.819 AC: 2848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.58
PhyloP100		-0.39
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: rs1404908; hg19: chr7-55262627;