rs56183713

Variant names:

• chr7-55181466-G-A
• rs56183713
• NM_005228.5:c.2457G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55181466-G-A
• chr7-55181466-G-C
• chr7-55181466-G-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3 BP6_Very_Strong BS1

The NM_005228.5(EGFR):​c.2457G>A​(p.Val819Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,614,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: EGFR NM_005228.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.70
• Publications: 18 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 -11 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 7-55181466-G-A is Benign according to our data. Variant chr7-55181466-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000144 (22/152364) while in subpopulation EAS AF = 0.00386 (20/5186). AF 95% confidence interval is 0.00255. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.2457G>A	p.Val819Val	synonymous	Exon 20 of 28	NP_005219.2
	EGFR	NM_001346899.2		c.2322G>A	p.Val774Val	synonymous	Exon 19 of 27	NP_001333828.1
	EGFR	NM_001346900.2		c.2298G>A	p.Val766Val	synonymous	Exon 20 of 28	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.2457G>A	p.Val819Val	synonymous	Exon 20 of 28	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.2322G>A	p.Val774Val	synonymous	Exon 19 of 26	ENSP00000415559.1	Q504U8
	EGFR	ENST00000898199.1		c.2448G>A	p.Val816Val	synonymous	Exon 20 of 28	ENSP00000568258.1

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000465 AC: 117 AN: 251450 AF XY: 0.000412

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00593

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000189 AC: 277 AN: 1461892 Hom.: 0 Cov.: 33 AF XY: 0.000180 AC XY: 131 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00529 AC: 210 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1112012

Other (OTH) AF: 0.000199 AC: 12 AN: 60396

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152364 Hom.: 0 Cov.: 33 AF XY: 0.000174 AC XY: 13 AN XY: 74516

African (AFR) AF: 0.00 AC: 0 AN: 41596

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000215

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Lung cancer (2)
-	-	2	not provided (2)
-	-	1	EGFR-related lung cancer (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Benign	0.91
PhyloP100		2.7
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.53		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.53		Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56183713; hg19: chr7-55249159;