dbSNP rs17337135: EGFR:c.2283+69G>A (chr7-55174889-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005228.5(EGFR):c.2283+69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,243,416 control chromosomes in the GnomAD database, including 389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 33 hom., cov: 33)

Exomes 𝑓: 0.023 ( 356 hom. )

Consequence

EGFR
NM_005228.5 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.724

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-55174889-G-A is Benign according to our data. Variant chr7-55174889-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1191430.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 = 0.0192 (2931/152286) while in subpopulation NFE AF= 0.0276 (1880/68030). AF 95% confidence interval is 0.0266. There are 33 homozygotes in gnomad4. There are 1311 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5 link	c.2283+69G>A		intron_variant	Intron 19 of 27	ENST00000275493.7	NP_005219.2	P00533-1Q504U8F2YGG7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EGFR	ENST00000275493.7 link	c.2283+69G>A	intron_variant	Intron 19 of 27	1	NM_005228.5	ENSP00000275493.2	P00533-1
EGFR	ENST00000455089.5 link	c.2148+69G>A	intron_variant	Intron 18 of 25	1		ENSP00000415559.1	Q504U8
EGFR	ENST00000450046.2 link	c.2124+69G>A	intron_variant	Intron 19 of 27	4		ENSP00000413354.2	C9JYS6
EGFR	ENST00000700145.1 link	c.630+69G>A	intron_variant	Intron 6 of 8			ENSP00000514824.1	A0A8V8TPW8

Frequencies

GnomAD3 genomes

AF:

0.0193

AC:

2935

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00990

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.0383

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0149

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0277

Gnomad OTH

AF:

0.0254

GnomAD4 exome

AF:

0.0227

AC:

24725

AN:

1091130

Hom.:

356

AF XY:

0.0227

AC XY:

12685

AN XY:

559150

show subpopulations

Gnomad4 AFR exome

AF:

0.00934

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.0334

Gnomad4 EAS exome

AF:

0.0000264

Gnomad4 SAS exome

AF:

0.0156

Gnomad4 FIN exome

AF:

0.00885

Gnomad4 NFE exome

AF:

0.0257

Gnomad4 OTH exome

AF:

0.0245

GnomAD4 genome

AF:

0.0192

AC:

2931

AN:

152286

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1311

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00984

Gnomad4 AMR

AF:

0.0182

Gnomad4 ASJ

AF:

0.0383

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.0276

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0279

Hom.:

Bravo

AF:

0.0202

Asia WGS

AF:

0.00925

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 16, 2019

GeneDx

Significance: Likely 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

-0.79

CADD

Benign

3.9

DANN

Benign

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over