rs13234622

Variant names:

• chr7-55144186-A-G
• rs13234622
• NM_005228.5:c.424+698A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-55144186-A-G
• chr7-55144186-A-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.424+698A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,080 control chromosomes in the GnomAD database, including 8,234 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 0.31 (8234 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• 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 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 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.424+698A>G		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.424+698A>G		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.265+698A>G		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.424+698A>G		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.424+698A>G		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000344576.7	TSL:1	c.424+698A>G		intron	N/A	ENSP00000345973.2	P00533-3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46593 AN: 151962 Hom.: 8248 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.306 AC: 46574 AN: 152080 Hom.: 8234 Cov.: 32 AF XY: 0.312 AC XY: 23199 AN XY: 74338

African (AFR) AF: 0.149 AC: 6191 AN: 41516

American (AMR) AF: 0.367 AC: 5608 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3468

East Asian (EAS) AF: 0.676 AC: 3484 AN: 5156

South Asian (SAS) AF: 0.353 AC: 1696 AN: 4808

European-Finnish (FIN) AF: 0.355 AC: 3753 AN: 10558

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.351 AC: 23844 AN: 67970

Other (OTH) AF: 0.321 AC: 677 AN: 2110

Alfa AF: 0.332 Hom.: 11476

Bravo AF: 0.301

Asia WGS AF: 0.464 AC: 1609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.32
PhyloP100		-0.30
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: rs13234622; hg19: chr7-55211879;