Genetic Variant EGFL7:p.Arg25Gln (chr9-136668356-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016215.5(EGFL7):c.74G>A(p.Arg25Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000619 in 1,598,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

EGFL7
NM_016215.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.235

Publications

0 publications found

Variant links:

COSMIC-nc: COSV100452042

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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07332459).

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.74G>A	p.Arg25Gln	missense	Exon 4 of 11	NP_057299.1	Q9UHF1
EGFL7	NM_201446.3		c.74G>A	p.Arg25Gln	missense	Exon 2 of 9	NP_958854.1	Q9UHF1
EGFL7	NR_045110.2		n.400G>A		non_coding_transcript_exon	Exon 3 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFL7	ENST00000308874.12	TSL:1 MANE Select	c.74G>A	p.Arg25Gln	missense	Exon 4 of 11	ENSP00000307843.7	Q9UHF1
EGFL7	ENST00000371698.3	TSL:1	c.74G>A	p.Arg25Gln	missense	Exon 2 of 9	ENSP00000360763.3	Q9UHF1
EGFL7	ENST00000406555.7	TSL:1	c.74G>A	p.Arg25Gln	missense	Exon 3 of 10	ENSP00000385639.3	Q9UHF1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000787

AC:

AN:

228832

AF XY:

0.0000884

show subpopulations

Gnomad AFR exome

AF:

0.000472

Gnomad AMR exome

AF:

0.000275

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000196

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000408

AC:

AN:

1445916

Hom.:

Cov.:

AF XY:

0.0000460

AC XY:

AN XY:

717862

show subpopulations

African (AFR)

AF:

0.000421

AC:

AN:

33216

American (AMR)

AF:

0.000207

AC:

AN:

43382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25328

East Asian (EAS)

AF:

0.00

AC:

AN:

39446

South Asian (SAS)

AF:

0.0000951

AC:

AN:

84132

European-Finnish (FIN)

AF:

0.0000391

AC:

AN:

51158

Middle Eastern (MID)

AF:

0.000361

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

0.0000136

AC:

AN:

1104130

Other (OTH)

AF:

0.000151

AC:

AN:

59582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000263

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.000818

AC:

AN:

41566

American (AMR)

AF:

0.000261

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68004

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

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:

0.0000992

Hom.:

Bravo

AF:

0.000253

ESP6500AA

AF:

0.000458

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000582

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.82

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.073

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.7

PhyloP100

0.23

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.53

REVEL

Benign

0.18

Sift

Benign

0.084

Sift4G

Benign

0.13

Polyphen

0.17

Vest4

0.27

MVP

0.94

MPC

0.13

ClinPred

0.030

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.058

gMVP

0.53

Mutation Taster

=82/18

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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