7-55173189-G-A

Variant names:

• chr7-55173189-G-A
• rs17290301
• NM_005228.5:c.2061+65G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005228.5(EGFR):​c.2061+65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,592,892 control chromosomes in the GnomAD database, including 503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (34 hom., cov: 33)
  • Exomes 𝑓: 0.024 (469 hom.)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42
• 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• neonatal inflammatory skin and bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-55173189-G-A is Benign according to our data. Variant chr7-55173189-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1174198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0199 (3034/152360) while in subpopulation NFE AF = 0.0281 (1915/68032). AF 95% confidence interval is 0.0271. There are 34 homozygotes in GnomAd4. There are 1368 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2061+65G>A		intron_variant	Intron 17 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2061+65G>A		intron_variant	Intron 17 of 27	1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000455089.5	c.1926+65G>A		intron_variant	Intron 16 of 25	1		ENSP00000415559.1
EGFR	ENST00000450046.2	c.1902+65G>A		intron_variant	Intron 17 of 27	4		ENSP00000413354.2
EGFR	ENST00000700145.1	c.408+65G>A		intron_variant	Intron 4 of 8			ENSP00000514824.1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3039 AN: 152242 Hom.: 34 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0282

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0240 AC: 34603 AN: 1440532 Hom.: 469 AF XY: 0.0240 AC XY: 17167 AN XY: 715922

African (AFR) AF: 0.0102 AC: 338 AN: 33230

American (AMR) AF: 0.0174 AC: 772 AN: 44394

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 933 AN: 25950

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39556

South Asian (SAS) AF: 0.0159 AC: 1365 AN: 85938

European-Finnish (FIN) AF: 0.00920 AC: 382 AN: 41520

Middle Eastern (MID) AF: 0.0449 AC: 204 AN: 4544

European-Non Finnish (NFE) AF: 0.0263 AC: 29052 AN: 1105598

Other (OTH) AF: 0.0260 AC: 1552 AN: 59802

GnomAD4 genome AF: 0.0199 AC: 3034 AN: 152360 Hom.: 34 Cov.: 33 AF XY: 0.0184 AC XY: 1368 AN XY: 74504

African (AFR) AF: 0.0104 AC: 431 AN: 41594

American (AMR) AF: 0.0203 AC: 310 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0153 AC: 74 AN: 4826

European-Finnish (FIN) AF: 0.00697 AC: 74 AN: 10620

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0281 AC: 1915 AN: 68032

Other (OTH) AF: 0.0260 AC: 55 AN: 2116

Alfa AF: 0.0154 Hom.: 8

Bravo AF: 0.0209

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 16, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.49
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism

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: rs17290301; hg19: chr7-55240882; COSMIC: COSV51791258;