rs1050171

Variant names:

• chr7-55181370-G-A
• rs1050171
• NM_005228.5:c.2361G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55181370-G-A
• chr7-55181370-G-T
• chr7-55181370-G-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_005228.5(EGFR):​c.2361G>A​(p.Gln787Gln) variant causes a synonymous change. The variant allele was found at a frequency of 0.558 in 1,613,948 control chromosomes in the GnomAD database, including 257,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (21009 hom., cov: 33)
  • Exomes 𝑓: 0.56 (236892 hom.)
• Consequence: EGFR NM_005228.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 4.23
• Publications: 217 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 7-55181370-G-A is Benign according to our data. Variant chr7-55181370-G-A is described in ClinVar as Benign. ClinVar VariationId is 45271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 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.2361G>A	p.Gln787Gln	synonymous	Exon 20 of 28	NP_005219.2
	EGFR	NM_001346899.2		c.2226G>A	p.Gln742Gln	synonymous	Exon 19 of 27	NP_001333828.1
	EGFR	NM_001346900.2		c.2202G>A	p.Gln734Gln	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.2361G>A	p.Gln787Gln	synonymous	Exon 20 of 28	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.2226G>A	p.Gln742Gln	synonymous	Exon 19 of 26	ENSP00000415559.1	Q504U8
	EGFR	ENST00000898199.1		c.2352G>A	p.Gln784Gln	synonymous	Exon 20 of 28	ENSP00000568258.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78151 AN: 151962 Hom.: 20991 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.548

GnomAD2 exomes AF: 0.524 AC: 131687 AN: 251430 AF XY: 0.530

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.172

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.590

Gnomad OTH exome AF: 0.585

GnomAD4 exome AF: 0.563 AC: 822502 AN: 1461868 Hom.: 236892 Cov.: 76 AF XY: 0.563 AC XY: 409475 AN XY: 727240

African (AFR) AF: 0.400 AC: 13385 AN: 33480

American (AMR) AF: 0.557 AC: 24902 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 17423 AN: 26136

East Asian (EAS) AF: 0.162 AC: 6420 AN: 39698

South Asian (SAS) AF: 0.508 AC: 43778 AN: 86258

European-Finnish (FIN) AF: 0.470 AC: 25129 AN: 53410

Middle Eastern (MID) AF: 0.612 AC: 3526 AN: 5766

European-Non Finnish (NFE) AF: 0.589 AC: 654708 AN: 1112000

Other (OTH) AF: 0.550 AC: 33231 AN: 60396

GnomAD4 genome AF: 0.514 AC: 78200 AN: 152080 Hom.: 21009 Cov.: 33 AF XY: 0.505 AC XY: 37542 AN XY: 74352

African (AFR) AF: 0.412 AC: 17085 AN: 41472

American (AMR) AF: 0.554 AC: 8474 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2292 AN: 3466

East Asian (EAS) AF: 0.177 AC: 914 AN: 5164

South Asian (SAS) AF: 0.480 AC: 2315 AN: 4820

European-Finnish (FIN) AF: 0.461 AC: 4877 AN: 10580

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40375 AN: 67978

Other (OTH) AF: 0.550 AC: 1160 AN: 2108

Alfa AF: 0.565 Hom.: 22929

Bravo AF: 0.517

Asia WGS AF: 0.371 AC: 1291 AN: 3478

EpiCase AF: 0.618

EpiControl AF: 0.604

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Lung cancer (2)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	EGFR-related lung cancer (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Inflammatory skin and bowel disease, neonatal, 2 (1)
-	-	1	Lung carcinoma (1)
-	-	1	Squamous cell lung carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	18
DANN	Benign	0.94
PhyloP100		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	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: rs1050171; hg19: chr7-55249063; COSMIC: COSV51769407;