7-55181237-C-G

Variant names:

• chr7-55181237-C-G
• rs41323247
• NM_005228.5:c.2284-56C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005228.5(EGFR):​c.2284-56C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,357,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.2284-56C>G		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.2149-56C>G		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.2125-56C>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.2284-56C>G		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.2149-56C>G		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000898199.1		c.2275-56C>G		intron	N/A	ENSP00000568258.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00107 AC: 1453 AN: 1357164 Hom.: 0 Cov.: 28 AF XY: 0.000959 AC XY: 652 AN XY: 679840

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

African (AFR) AF: 0.000861 AC: 27 AN: 31376

American (AMR) AF: 0.0000673 AC: 3 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.000314 AC: 8 AN: 25484

East Asian (EAS) AF: 0.000332 AC: 13 AN: 39100

South Asian (SAS) AF: 0.000417 AC: 35 AN: 83988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53004

Middle Eastern (MID) AF: 0.000208 AC: 1 AN: 4798

European-Non Finnish (NFE) AF: 0.00130 AC: 1319 AN: 1017978

Other (OTH) AF: 0.000827 AC: 47 AN: 56856

⚠️ 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 Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.56
DANN	Benign	0.64
PhyloP100		-2.1

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: rs41323247; hg19: chr7-55248930;