rs884419

Variant names:

• chr7-55208587-G-A
• rs884419
• NM_005228.5:c.*2970G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55208587-G-A
• chr7-55208587-G-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.*2970G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 152,040 control chromosomes in the GnomAD database, including 1,439 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 0.11 (1438 hom., cov: 31)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.*2970G>A		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.*2970G>A		3_prime_UTR_variant	Exon 28 of 28	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000450046.2	c.*2970G>A		3_prime_UTR_variant	Exon 28 of 28	4		ENSP00000413354.2
EGFR-AS1	ENST00000836806.1	n.207+4176C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17474 AN: 151900 Hom.: 1440 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0807

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0973

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0899

Gnomad OTH AF: 0.125

GnomAD4 exome AF: 0.136 AC: 3 AN: 22 Hom.: 1 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 1 AN: 10

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.115 AC: 17481 AN: 152018 Hom.: 1438 Cov.: 31 AF XY: 0.119 AC XY: 8812 AN XY: 74302

African (AFR) AF: 0.113 AC: 4704 AN: 41452

American (AMR) AF: 0.107 AC: 1630 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 280 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2365 AN: 5130

South Asian (SAS) AF: 0.200 AC: 964 AN: 4812

European-Finnish (FIN) AF: 0.0973 AC: 1027 AN: 10560

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0899 AC: 6111 AN: 67994

Other (OTH) AF: 0.125 AC: 264 AN: 2110

Alfa AF: 0.0951 Hom.: 111

Bravo AF: 0.120

Asia WGS AF: 0.268 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.51
PhyloP100		0.041
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: rs884419; hg19: chr7-55276280;