rs12538371

Variant names:

• chr7-55168327-T-C
• rs12538371
• NM_005228.5:c.1881-2848T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005228.5(EGFR):​c.1881-2848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 152,308 control chromosomes in the GnomAD database, including 868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.088 (868 hom., cov: 33)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.894
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 7-55168327-T-C is Benign according to our data. Variant chr7-55168327-T-C is described in ClinVar as Benign. ClinVar VariationId is 1287799.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.178 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.1881-2848T>C		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.1746-2848T>C		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.1722-2848T>C		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.1881-2848T>C		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.1746-2848T>C		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000344576.7	TSL:1	c.1881-1980T>C		intron	N/A	ENSP00000345973.2	P00533-3

Frequencies

GnomAD3 genomes AF: 0.0879 AC: 13382 AN: 152190 Hom.: 858 Cov.: 33

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.00326

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.0870

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

GnomAD4 genome AF: 0.0880 AC: 13409 AN: 152308 Hom.: 868 Cov.: 33 AF XY: 0.0876 AC XY: 6528 AN XY: 74480

African (AFR) AF: 0.0347 AC: 1442 AN: 41570

American (AMR) AF: 0.184 AC: 2809 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0965 AC: 335 AN: 3470

East Asian (EAS) AF: 0.00327 AC: 17 AN: 5196

South Asian (SAS) AF: 0.107 AC: 514 AN: 4826

European-Finnish (FIN) AF: 0.0918 AC: 975 AN: 10620

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6986 AN: 68018

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0971 Hom.: 481

Bravo AF: 0.0939

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.43
PhyloP100		-0.89
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: rs12538371; hg19: chr7-55236020;