Variant chr9-136669940-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016215.5(EGFL7):c.340G>A(p.Gly114Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000554 in 1,605,494 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 3 hom. )

Consequence

EGFL7
NM_016215.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.49

Variant links:

Genes affected

EGFL7 (HGNC:20594): (EGF like domain multiple 7) This gene encodes a secreted endothelial cell protein that contains two epidermal growth factor-like domains. The encoded protein may play a role in regulating vasculogenesis. This protein may be involved in the growth and proliferation of tumor cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

EGFL7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01774624).

BP6

Variant 9-136669940-G-A is Benign according to our data. Variant chr9-136669940-G-A is described in ClinVar as [Benign]. Clinvar id is 716928.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL7	NM_016215.5 link	c.340G>A	p.Gly114Arg	missense_variant	7/11	ENST00000308874.12	NP_057299.1	Q9UHF1A0A024R8F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFL7	ENST00000308874.12 link	c.340G>A	p.Gly114Arg	missense_variant	7/11	1	NM_016215.5	ENSP00000307843.7		Q9UHF1

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

420

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00984

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000678

AC:

159

AN:

234344

Hom.:

AF XY:

0.000492

AC XY:

AN XY:

128154

show subpopulations

Gnomad AFR exome

AF:

0.0101

Gnomad AMR exome

AF:

0.000210

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000478

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.000322

AC:

468

AN:

1453128

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

183

AN XY:

722332

show subpopulations

Gnomad4 AFR exome

AF:

0.0117

Gnomad4 AMR exome

AF:

0.000205

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000352

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000262

Gnomad4 OTH exome

AF:

0.000617

GnomAD4 genome

AF:

0.00277

AC:

422

AN:

152366

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00986

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00320

ESP6500AA

AF:

0.0103

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000881

AC:

106

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

D;D;D;D

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;D;.;.

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.3

M;M;M;M

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-7.0

D;D;D;D

REVEL

Benign

0.25

Sift

Benign

0.035

D;D;D;D

Sift4G

Uncertain

0.050

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.63

MutPred

0.36

Gain of phosphorylation at S116 (P = 0.1138);Gain of phosphorylation at S116 (P = 0.1138);Gain of phosphorylation at S116 (P = 0.1138);Gain of phosphorylation at S116 (P = 0.1138);

MVP

0.73

MPC

0.57

ClinPred

0.11

GERP RS

4.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.31

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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