Genetic Variant EGFL7:p.Gly114Arg (chr9-136669940-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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 (★).

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

Publications

1 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 716928.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016215.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFL7	NM_016215.5	MANE Select	c.340G>A	p.Gly114Arg	missense	Exon 7 of 11	NP_057299.1	Q9UHF1
EGFL7	NM_201446.3		c.340G>A	p.Gly114Arg	missense	Exon 5 of 9	NP_958854.1	Q9UHF1
EGFL7	NR_045110.2		n.666G>A		non_coding_transcript_exon	Exon 6 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFL7	ENST00000308874.12	TSL:1 MANE Select	c.340G>A	p.Gly114Arg	missense	Exon 7 of 11	ENSP00000307843.7	Q9UHF1
EGFL7	ENST00000371698.3	TSL:1	c.340G>A	p.Gly114Arg	missense	Exon 5 of 9	ENSP00000360763.3	Q9UHF1
EGFL7	ENST00000406555.7	TSL:1	c.340G>A	p.Gly114Arg	missense	Exon 6 of 10	ENSP00000385639.3	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

GnomAD2 exomes

AF:

0.000678

AC:

159

AN:

234344

AF XY:

0.000492

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 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

African (AFR)

AF:

0.0117

AC:

388

AN:

33286

American (AMR)

AF:

0.000205

AC:

AN:

43960

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25906

East Asian (EAS)

AF:

0.00

AC:

AN:

39342

South Asian (SAS)

AF:

0.0000352

AC:

AN:

85136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51378

Middle Eastern (MID)

AF:

0.000366

AC:

AN:

5468

European-Non Finnish (NFE)

AF:

0.0000262

AC:

AN:

1108698

Other (OTH)

AF:

0.000617

AC:

AN:

59954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00277

AC:

422

AN:

152366

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00986

AC:

410

AN:

41590

American (AMR)

AF:

0.000392

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68034

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00147

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.3

PhyloP100

4.5

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-7.0

REVEL

Benign

0.25

Sift

Benign

0.035

Sift4G

Uncertain

0.050

Polyphen

1.0

Vest4

0.63

MutPred

0.36

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

Mutation Taster

=46/54

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over