rs1357973

Variant names:

• chr7-55211587-C-A
• rs1357973
• NM_005228.5:c.*5970C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55211587-C-A
• chr7-55211587-C-G
• chr7-55211587-C-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.*5970C>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 0.906 in 152,254 control chromosomes in the GnomAD database, including 62,586 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 0.91 (62586 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: EGFR NM_005228.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.*5970C>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.*5970C>A		3_prime_UTR_variant	Exon 28 of 28	1	NM_005228.5	ENSP00000275493.2
EGFR-AS1	ENST00000836806.1	n.207+1176G>T		intron_variant	Intron 1 of 1
EGFR	ENST00000450046.2	c.*5970C>A		downstream_gene_variant		4		ENSP00000413354.2

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137750 AN: 152136 Hom.: 62526 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.889

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.899

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.906 AC: 137869 AN: 152254 Hom.: 62586 Cov.: 33 AF XY: 0.910 AC XY: 67733 AN XY: 74448

African (AFR) AF: 0.968 AC: 40232 AN: 41546

American (AMR) AF: 0.904 AC: 13831 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3125 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4838 AN: 5188

South Asian (SAS) AF: 0.946 AC: 4564 AN: 4826

European-Finnish (FIN) AF: 0.889 AC: 9421 AN: 10602

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58934 AN: 67998

Other (OTH) AF: 0.899 AC: 1902 AN: 2116

Alfa AF: 0.888 Hom.: 7769

Bravo AF: 0.909

Asia WGS AF: 0.933 AC: 3236 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.066
DANN	Benign	0.42
PhyloP100		-0.93
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: rs1357973; hg19: chr7-55279280;