rs2330951

Variant names:

• chr7-55106649-C-A
• rs2330951
• NM_005228.5:c.89-35637C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-55106649-C-A
• chr7-55106649-C-T

Variant summary

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

The NM_005228.5(EGFR):​c.89-35637C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 152,172 control chromosomes in the GnomAD database, including 49,622 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 0.80 (49622 hom., cov: 32)
• Consequence: EGFR NM_005228.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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=-1.08).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.89-35637C>A		intron_variant	Intron 1 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.89-35637C>A		intron_variant	Intron 1 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122337 AN: 152054 Hom.: 49589 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.805 AC: 122424 AN: 152172 Hom.: 49622 Cov.: 32 AF XY: 0.808 AC XY: 60094 AN XY: 74402

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.743

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.819

Alfa AF: 0.773 Hom.: 63706

Bravo AF: 0.807

Asia WGS AF: 0.922 AC: 3204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.049
DANN	Benign	0.18

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: rs2330951; hg19: chr7-55174342;