chr7-55192070-A-G

Variant names:

• chr7-55192070-A-G
• rs6970262
• NM_005228.5:c.2625+196A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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-AS1 (HGNC:40207): (EGFR antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005228.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	NM_005228.5	MANE Select	c.2625+196A>G		intron	N/A	NP_005219.2
	EGFR	NM_001346899.2		c.2490+196A>G		intron	N/A	NP_001333828.1
	EGFR	NM_001346900.2		c.2466+196A>G		intron	N/A	NP_001333829.1	C9JYS6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFR	ENST00000275493.7	TSL:1 MANE Select	c.2625+196A>G		intron	N/A	ENSP00000275493.2	P00533-1
	EGFR	ENST00000455089.5	TSL:1	c.2490+196A>G		intron	N/A	ENSP00000415559.1	Q504U8
	EGFR	ENST00000898199.1		c.2616+196A>G		intron	N/A	ENSP00000568258.1

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

African (AFR) AF: 0.673 AC: 27904 AN: 41440

American (AMR) AF: 0.692 AC: 10579 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1930 AN: 3470

East Asian (EAS) AF: 0.894 AC: 4579 AN: 5120

South Asian (SAS) AF: 0.840 AC: 4040 AN: 4812

European-Finnish (FIN) AF: 0.690 AC: 7283 AN: 10562

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42300 AN: 67960

Other (OTH) AF: 0.634 AC: 1339 AN: 2112

Alfa AF: 0.637 Hom.: 104593

Bravo AF: 0.662

Asia WGS AF: 0.841 AC: 2923 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.30
DANN	Benign	0.49
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs6970262; hg19: chr7-55259763;