rs17336437

Variant names:

• chr7-55146712-G-A
• rs17336437
• NM_005228.5:c.531G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55146712-G-A
• chr7-55146712-G-C
• chr7-55146712-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_005228.5(EGFR):​c.531G>A​(p.Ser177Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,614,128 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S177S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.019 (91 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (87 hom.)
• Consequence: EGFR NM_005228.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -4.04
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-55146712-G-A is Benign according to our data. Variant chr7-55146712-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 360455.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.066 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.531G>A	p.Ser177Ser	synonymous	Exon 4 of 28	NP_005219.2
	EGFR	NM_001346900.2		c.372G>A	p.Ser124Ser	synonymous	Exon 4 of 28	NP_001333829.1	C9JYS6
	EGFR	NM_001346898.2		c.531G>A	p.Ser177Ser	synonymous	Exon 4 of 27	NP_001333827.1	E7BSV0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.531G>A	p.Ser177Ser	synonymous	Exon 4 of 28	ENSP00000275493.2	P00533-1
	EGFR	ENST00000344576.7	TSL:1	c.531G>A	p.Ser177Ser	synonymous	Exon 4 of 16	ENSP00000345973.2	P00533-3
	EGFR	ENST00000342916.7	TSL:1	c.531G>A	p.Ser177Ser	synonymous	Exon 4 of 16	ENSP00000342376.3	P00533-4

Frequencies

GnomAD3 genomes AF: 0.0195 AC: 2963 AN: 152134 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0682

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00535 AC: 1346 AN: 251416 AF XY: 0.00400

Gnomad AFR exome AF: 0.0719

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00208 AC: 3041 AN: 1461876 Hom.: 87 Cov.: 36 AF XY: 0.00182 AC XY: 1324 AN XY: 727240

African (AFR) AF: 0.0728 AC: 2439 AN: 33480

American (AMR) AF: 0.00418 AC: 187 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000344 AC: 9 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.0000980 AC: 109 AN: 1112012

Other (OTH) AF: 0.00431 AC: 260 AN: 60394

GnomAD4 genome AF: 0.0195 AC: 2966 AN: 152252 Hom.: 91 Cov.: 33 AF XY: 0.0188 AC XY: 1402 AN XY: 74450

African (AFR) AF: 0.0681 AC: 2828 AN: 41520

American (AMR) AF: 0.00588 AC: 90 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68024

Other (OTH) AF: 0.0156 AC: 33 AN: 2116

Alfa AF: 0.00499 Hom.: 17

Bravo AF: 0.0228

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	EGFR-related lung cancer (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	Lung cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.33
DANN	Benign	0.54
PhyloP100		-4.0
Mutation Taster		=94/6	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: rs17336437; hg19: chr7-55214405;