Genetic Variant NM_016215.5:c.598G>C (chr9-136670976-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016215.5(EGFL7):c.598G>C(p.Val200Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000333 in 1,502,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

EGFL7
NM_016215.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.588

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08652055).

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.598G>C	p.Val200Leu	missense	Exon 9 of 11	NP_057299.1	Q9UHF1
EGFL7	NM_201446.3		c.598G>C	p.Val200Leu	missense	Exon 7 of 9	NP_958854.1	Q9UHF1
EGFL7	NR_045110.2		n.924G>C		non_coding_transcript_exon	Exon 8 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFL7	ENST00000308874.12	TSL:1 MANE Select	c.598G>C	p.Val200Leu	missense	Exon 9 of 11	ENSP00000307843.7	Q9UHF1
EGFL7	ENST00000371698.3	TSL:1	c.598G>C	p.Val200Leu	missense	Exon 7 of 9	ENSP00000360763.3	Q9UHF1
EGFL7	ENST00000406555.7	TSL:1	c.598G>C	p.Val200Leu	missense	Exon 8 of 10	ENSP00000385639.3	Q9UHF1

Frequencies

GnomAD3 genomes

AF:

0.00000705

AC:

AN:

141924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000294

AC:

AN:

1360858

Hom.:

Cov.:

AF XY:

0.00000446

AC XY:

AN XY:

672612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30050

American (AMR)

AF:

0.00

AC:

AN:

36250

Ashkenazi Jewish (ASJ)

AF:

0.000125

AC:

AN:

24078

East Asian (EAS)

AF:

0.00

AC:

AN:

22042

South Asian (SAS)

AF:

0.00

AC:

AN:

79914

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43782

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5448

European-Non Finnish (NFE)

AF:

9.40e-7

AC:

AN:

1064164

Other (OTH)

AF:

0.00

AC:

AN:

55130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00000705

AC:

AN:

141924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38008

American (AMR)

AF:

0.00

AC:

AN:

13696

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

3952

South Asian (SAS)

AF:

0.00

AC:

AN:

4272

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8844

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66540

Other (OTH)

AF:

0.00

AC:

AN:

1974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

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:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.20

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.098

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.2

PhyloP100

0.59

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.3

REVEL

Benign

0.21

Sift

Benign

0.033

Sift4G

Benign

0.082

Polyphen

0.0020

Vest4

0.31

MutPred

0.25

Gain of loop (P = 0.1081)

MVP

0.54

MPC

0.11

ClinPred

0.25

GERP RS

1.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.7

Varity_R

0.077

gMVP

0.33

Mutation Taster

=90/10

polymorphism

(source)

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

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