chr7-55170575-G-A

Variant names:

• chr7-55170575-G-A
• rs10228436
• ENST00000344576.7:c.*31G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_201284.2(EGFR):​c.*31G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,610,342 control chromosomes in the GnomAD database, including 100,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (8535 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92134 hom.)
• Consequence: EGFR NM_201284.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.22

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 7-55170575-G-A is Benign according to our data. Variant chr7-55170575-G-A is described in ClinVar as [Benign]. Clinvar id is 1289672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFR	NM_005228.5	c.1881-600G>A		intron_variant	Intron 15 of 27	ENST00000275493.7	NP_005219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFR	ENST00000275493.7	c.1881-600G>A		intron_variant	Intron 15 of 27	1	NM_005228.5	ENSP00000275493.2

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49272 AN: 151754 Hom.: 8538 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.358

GnomAD2 exomes AF: 0.371 AC: 92479 AN: 249574 AF XY: 0.375

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.391

Gnomad ASJ exome AF: 0.483

Gnomad EAS exome AF: 0.539

Gnomad FIN exome AF: 0.313

Gnomad NFE exome AF: 0.343

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.350 AC: 510302 AN: 1458470 Hom.: 92134 Cov.: 60 AF XY: 0.353 AC XY: 256083 AN XY: 725752

Gnomad4 AFR exome AF: 0.226 AC: 7548 AN: 33466

Gnomad4 AMR exome AF: 0.389 AC: 17411 AN: 44722

Gnomad4 ASJ exome AF: 0.488 AC: 12754 AN: 26134

Gnomad4 EAS exome AF: 0.603 AC: 23952 AN: 39700

Gnomad4 SAS exome AF: 0.424 AC: 36535 AN: 86220

Gnomad4 FIN exome AF: 0.312 AC: 15736 AN: 50492

Gnomad4 NFE exome AF: 0.334 AC: 371297 AN: 1111964

Gnomad4 Remaining exome AF: 0.374 AC: 22568 AN: 60324

GnomAD4 genome AF: 0.324 AC: 49277 AN: 151872 Hom.: 8535 Cov.: 32 AF XY: 0.329 AC XY: 24407 AN XY: 74234

Gnomad4 AFR AF: 0.231 AC: 0.231414 AN: 0.231414

Gnomad4 AMR AF: 0.361 AC: 0.361235 AN: 0.361235

Gnomad4 ASJ AF: 0.476 AC: 0.476369 AN: 0.476369

Gnomad4 EAS AF: 0.552 AC: 0.551958 AN: 0.551958

Gnomad4 SAS AF: 0.439 AC: 0.439167 AN: 0.439167

Gnomad4 FIN AF: 0.313 AC: 0.313234 AN: 0.313234

Gnomad4 NFE AF: 0.339 AC: 0.339458 AN: 0.339458

Gnomad4 OTH AF: 0.359 AC: 0.35884 AN: 0.35884

Alfa AF: 0.344 Hom.: 36749

Bravo AF: 0.328

Asia WGS AF: 0.475 AC: 1649 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.078
DANN	Benign	0.51
Mutation Taster		=10/90	disease causing

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: rs10228436; hg19: chr7-55238268; COSMIC: COSV51829087; COSMIC: COSV51829087;