7-55192070-A-G

Position:

• chr7-55192070-A-G

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.2625+196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,976 control chromosomes in the GnomAD database, including 33,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33752 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.264

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=-0.87).
• BP6: Variant 7-55192070-A-G is Benign according to our data. Variant chr7-55192070-A-G is described in ClinVar as [Benign]. Clinvar id is 1290215.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFR	NM_005228.5	c.2625+196A>G		intron_variant		ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.2625+196A>G		intron_variant		1	NM_005228.5	ENSP00000275493.2
EGFR	ENST00000455089.5	c.2490+196A>G		intron_variant		1		ENSP00000415559.1
EGFR	ENST00000450046.2	c.2466+196A>G		intron_variant		4		ENSP00000413354.2
EGFR	ENST00000700145.1	c.897+271A>G		intron_variant				ENSP00000514824.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100599 AN: 151858 Hom.: 33696 Cov.: 32

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.632

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

GnomAD4 genome AF: 0.663 AC: 100709 AN: 151976 Hom.: 33752 Cov.: 32 AF XY: 0.673 AC XY: 49956 AN XY: 74232

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.634

Alfa AF: 0.634 Hom.: 45877

Bravo AF: 0.662

Asia WGS AF: 0.841 AC: 2923 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	-0.87
CADD	Benign	0.30
DANN	Benign	0.49

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: rs6970262; hg19: chr7-55259763;