7-55049014-G-A

Position:

• chr7-55049014-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005228.5(EGFR):​c.88+29649G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 152,180 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.043 (270 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5	c.88+29649G>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7	c.88+29649G>A		intron_variant		1	NM_005228.5	P1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6543 AN: 152062 Hom.: 263 Cov.: 32

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.0686

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0336

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

GnomAD4 genome AF: 0.0432 AC: 6576 AN: 152180 Hom.: 270 Cov.: 32 AF XY: 0.0450 AC XY: 3346 AN XY: 74412

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.0680

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0109

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0291 Hom.: 19

Bravo AF: 0.0466

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
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

Other links and lift over

dbSNP: rs759165; hg19: chr7-55116707;