rs4947492

Variant names:

• chr7-55120299-G-A
• rs4947492
• NM_005228.5:c.89-21987G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55120299-G-A
• chr7-55120299-G-C
• chr7-55120299-G-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.89-21987G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,056 control chromosomes in the GnomAD database, including 20,005 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 0.50 (20005 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.398
• 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 Gene-Disease associations (from GenCC):

• lung cancer

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P, Ambry Genetics
• non-small cell lung carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• inflammatory skin and bowel disease, neonatal, 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• neonatal inflammatory skin and bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.89-21987G>A		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.89-21987G>A		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.-72+10341G>A		intron	N/A	NP_001333829.1	C9JYS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.89-21987G>A		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.89-21987G>A		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000344576.7	TSL:1	c.89-21987G>A		intron	N/A	ENSP00000345973.2	P00533-3

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76272 AN: 151938 Hom.: 20003 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.530

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.502 AC: 76301 AN: 152056 Hom.: 20005 Cov.: 32 AF XY: 0.505 AC XY: 37533 AN XY: 74304

African (AFR) AF: 0.346 AC: 14346 AN: 41480

American (AMR) AF: 0.628 AC: 9596 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3468

East Asian (EAS) AF: 0.694 AC: 3571 AN: 5142

South Asian (SAS) AF: 0.506 AC: 2433 AN: 4808

European-Finnish (FIN) AF: 0.530 AC: 5606 AN: 10580

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37459 AN: 67972

Other (OTH) AF: 0.505 AC: 1066 AN: 2110

Alfa AF: 0.530 Hom.: 9074

Bravo AF: 0.503

Asia WGS AF: 0.609 AC: 2117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.35
DANN	Benign	0.53
PhyloP100		-0.40
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: rs4947492; hg19: chr7-55187992;