7-55181094-T-C

Variant names:

• chr7-55181094-T-C
• rs10241326
• NM_005228.5:c.2284-199T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005228.5(EGFR):​c.2284-199T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 666,234 control chromosomes in the GnomAD database, including 108,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25517 hom., cov: 33)
  • Exomes 𝑓: 0.56 (82875 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.40
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-55181094-T-C is Benign according to our data. Variant chr7-55181094-T-C is described in ClinVar as [Benign]. Clinvar id is 1276464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2284-199T>C		intron_variant	Intron 19 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2284-199T>C		intron_variant	Intron 19 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86863 AN: 152012 Hom.: 25493 Cov.: 33

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.555 AC: 285506 AN: 514102 Hom.: 82875 Cov.: 6 AF XY: 0.555 AC XY: 149832 AN XY: 270042

African (AFR) AF: 0.601 AC: 8465 AN: 14074

American (AMR) AF: 0.565 AC: 13309 AN: 23558

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 9848 AN: 14720

East Asian (EAS) AF: 0.161 AC: 5070 AN: 31436

South Asian (SAS) AF: 0.512 AC: 25372 AN: 49580

European-Finnish (FIN) AF: 0.471 AC: 14355 AN: 30478

Middle Eastern (MID) AF: 0.655 AC: 1369 AN: 2090

European-Non Finnish (NFE) AF: 0.599 AC: 191722 AN: 319912

Other (OTH) AF: 0.566 AC: 15996 AN: 28254

GnomAD4 genome AF: 0.571 AC: 86941 AN: 152132 Hom.: 25517 Cov.: 33 AF XY: 0.560 AC XY: 41620 AN XY: 74380

African (AFR) AF: 0.604 AC: 25061 AN: 41504

American (AMR) AF: 0.583 AC: 8914 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2314 AN: 3470

East Asian (EAS) AF: 0.179 AC: 922 AN: 5156

South Asian (SAS) AF: 0.485 AC: 2341 AN: 4826

European-Finnish (FIN) AF: 0.462 AC: 4890 AN: 10594

Middle Eastern (MID) AF: 0.685 AC: 200 AN: 292

European-Non Finnish (NFE) AF: 0.596 AC: 40527 AN: 67968

Other (OTH) AF: 0.591 AC: 1249 AN: 2114

Alfa AF: 0.595 Hom.: 5450

Bravo AF: 0.584

Asia WGS AF: 0.397 AC: 1381 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.042
DANN	Benign	0.31
PhyloP100		-2.4
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: rs10241326; hg19: chr7-55248787;