rs6593211

Variant names:

• chr7-55210271-G-A
• rs6593211
• NM_005228.5:c.*4654G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55210271-G-A
• chr7-55210271-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.*4654G>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 0.378 in 152,004 control chromosomes in the GnomAD database, including 12,583 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 0.38 (12583 hom., cov: 33)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715
• Publications: 14 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.*4654G>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.*4654G>A		3_prime_UTR_variant	Exon 28 of 28	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000450046.2	c.*4654G>A		3_prime_UTR_variant	Exon 28 of 28	4		ENSP00000413354.2
EGFR-AS1	ENST00000836806.1	n.207+2492C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57341 AN: 151882 Hom.: 12551 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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

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: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.378 AC: 57422 AN: 152002 Hom.: 12583 Cov.: 33 AF XY: 0.386 AC XY: 28670 AN XY: 74300

African (AFR) AF: 0.559 AC: 23179 AN: 41434

American (AMR) AF: 0.309 AC: 4716 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3470

East Asian (EAS) AF: 0.748 AC: 3877 AN: 5180

South Asian (SAS) AF: 0.507 AC: 2439 AN: 4812

European-Finnish (FIN) AF: 0.348 AC: 3673 AN: 10544

Middle Eastern (MID) AF: 0.267 AC: 78 AN: 292

European-Non Finnish (NFE) AF: 0.261 AC: 17748 AN: 67968

Other (OTH) AF: 0.343 AC: 721 AN: 2104

Alfa AF: 0.304 Hom.: 22028

Bravo AF: 0.384

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.084
DANN	Benign	0.22
PhyloP100		-0.71
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: rs6593211; hg19: chr7-55277964;