Variant chr7-55173189-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005228.5(EGFR):c.2061+65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,592,892 control chromosomes in the GnomAD database, including 503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 34 hom., cov: 33)

Exomes 𝑓: 0.024 ( 469 hom. )

Consequence

EGFR
NM_005228.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.42

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-55173189-G-A is Benign according to our data. Variant chr7-55173189-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1174198.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 = 0.0199 (3034/152360) while in subpopulation NFE AF= 0.0281 (1915/68032). AF 95% confidence interval is 0.0271. There are 34 homozygotes in gnomad4. There are 1368 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFR	NM_005228.5 linkuse as main transcript	c.2061+65G>A		intron_variant		ENST00000275493.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
EGFR	ENST00000275493.7 linkuse as main transcript	c.2061+65G>A	intron_variant	1	NM_005228.5	P1	P00533-1
EGFR	ENST00000455089.5 linkuse as main transcript	c.1926+65G>A	intron_variant	1
EGFR	ENST00000450046.2 linkuse as main transcript	c.1902+65G>A	intron_variant	4
EGFR	ENST00000700145.1 linkuse as main transcript	c.410+65G>A	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0200

AC:

3039

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0203

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0282

Gnomad OTH

AF:

0.0263

GnomAD4 exome

AF:

0.0240

AC:

34603

AN:

1440532

Hom.:

469

AF XY:

0.0240

AC XY:

17167

AN XY:

715922

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.0174

Gnomad4 ASJ exome

AF:

0.0360

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0159

Gnomad4 FIN exome

AF:

0.00920

Gnomad4 NFE exome

AF:

0.0263

Gnomad4 OTH exome

AF:

0.0260

GnomAD4 genome

AF:

0.0199

AC:

3034

AN:

152360

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1368

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0104

Gnomad4 AMR

AF:

0.0203

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0153

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.0281

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0209

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.0

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

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