rs12538371

Positions:

• chr7-55168327-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1881-2848T>C		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.1881-2848T>C		intron_variant		1	NM_005228.5	ENSP00000275493	P1

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

Gnomad4 AFR AF: 0.0347

Gnomad4 AMR AF: 0.184

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.00327

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0918

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0984 Hom.: 192

Bravo AF: 0.0939

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs12538371; hg19: chr7-55236020; COSMIC: COSV51775010;