rs11569017

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001963.6(EGF):c.2351A>T(p.Asp784Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,613,974 control chromosomes in the GnomAD database, including 3,671 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 367 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3304 hom. )

Consequence

EGF
NM_001963.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

EGF (HGNC:3229): (epidermal growth factor) This gene encodes a member of the epidermal growth factor superfamily. The encoded preproprotein is proteolytically processed to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by binding with high affinity to the cell surface receptor, epidermal growth factor receptor. Defects in this gene are the cause of hypomagnesemia type 4. Dysregulation of this gene has been associated with the growth and progression of certain cancers. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

EGF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013268888).

BP6

Variant 4-109980955-A-T is Benign according to our data. Variant chr4-109980955-A-T is described in ClinVar as [Benign]. Clinvar id is 347246.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGF	NM_001963.6 link	c.2351A>T	p.Asp784Val	missense_variant	Exon 15 of 24	ENST00000265171.10	NP_001954.2	P01133-1
EGF	NM_001178130.3 link	c.2351A>T	p.Asp784Val	missense_variant	Exon 15 of 23		NP_001171601.1	P01133-3
EGF	NM_001178131.3 link	c.2225A>T	p.Asp742Val	missense_variant	Exon 14 of 23		NP_001171602.1	P01133-2
EGF	NM_001357021.2 link	c.2225A>T	p.Asp742Val	missense_variant	Exon 14 of 20		NP_001343950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGF	ENST00000265171.10 link	c.2351A>T	p.Asp784Val	missense_variant	Exon 15 of 24	1	NM_001963.6	ENSP00000265171.5		P01133-1

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8057

AN:

152082

Hom.:

367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.0798

Gnomad ASJ

AF:

0.0850

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.0711

Gnomad FIN

AF:

0.0465

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0574

Gnomad OTH

AF:

0.0612

GnomAD3 exomes

AF:

0.0733

AC:

18423

AN:

251416

Hom.:

881

AF XY:

0.0729

AC XY:

9899

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.0795

Gnomad EAS exome

AF:

0.187

Gnomad SAS exome

AF:

0.0757

Gnomad FIN exome

AF:

0.0537

Gnomad NFE exome

AF:

0.0572

Gnomad OTH exome

AF:

0.0701

GnomAD4 exome

AF:

0.0607

AC:

88719

AN:

1461774

Hom.:

3304

Cov.:

AF XY:

0.0612

AC XY:

44476

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00911

Gnomad4 AMR exome

AF:

0.0985

Gnomad4 ASJ exome

AF:

0.0793

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.0733

Gnomad4 FIN exome

AF:

0.0565

Gnomad4 NFE exome

AF:

0.0545

Gnomad4 OTH exome

AF:

0.0616

GnomAD4 genome

AF:

0.0530

AC:

8059

AN:

152200

Hom.:

367

Cov.:

AF XY:

0.0552

AC XY:

4108

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.0116

Gnomad4 AMR

AF:

0.0797

Gnomad4 ASJ

AF:

0.0850

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.0716

Gnomad4 FIN

AF:

0.0465

Gnomad4 NFE

AF:

0.0574

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0624

Hom.:

292

Bravo

AF:

0.0529

TwinsUK

AF:

0.0553

AC:

205

ALSPAC

AF:

0.0524

AC:

202

ESP6500AA

AF:

0.0134

AC:

ESP6500EA

AF:

0.0597

AC:

513

ExAC

AF:

0.0704

AC:

8552

Asia WGS

AF:

0.110

AC:

384

AN:

3478

EpiCase

AF:

0.0593

EpiControl

AF:

0.0581

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16574953) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Renal hypomagnesemia 4

Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.44

.;T;.

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.83

T;T;T

MetaRNN

Benign

0.0013

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L;L

PrimateAI

Benign

0.19

PROVEAN

Benign

-2.4

N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.0040

B;B;.

Vest4

0.18

MPC

0.26

ClinPred

0.013

GERP RS

3.7

Varity_R

0.50

gMVP

0.59

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