Genetic Variant EGFL7:p.Ala87Val (chr9-136669668-C-T) – 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.260C>T(p.Ala87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,609,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A87T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

EGFL7
NM_016215.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.648

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:

Genome browser will be placed here

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=0.10185751).

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.260C>T	p.Ala87Val	missense	Exon 6 of 11	NP_057299.1	Q9UHF1
EGFL7	NM_201446.3		c.260C>T	p.Ala87Val	missense	Exon 4 of 9	NP_958854.1	Q9UHF1
EGFL7	NR_045110.2		n.586C>T		non_coding_transcript_exon	Exon 5 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFL7	ENST00000308874.12	TSL:1 MANE Select	c.260C>T	p.Ala87Val	missense	Exon 6 of 11	ENSP00000307843.7	Q9UHF1
EGFL7	ENST00000371698.3	TSL:1	c.260C>T	p.Ala87Val	missense	Exon 4 of 9	ENSP00000360763.3	Q9UHF1
EGFL7	ENST00000406555.7	TSL:1	c.260C>T	p.Ala87Val	missense	Exon 5 of 10	ENSP00000385639.3	Q9UHF1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000293

AC:

AN:

239018

AF XY:

0.00000767

show subpopulations

Gnomad AFR exome

AF:

0.0000680

Gnomad AMR exome

AF:

0.000118

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000934

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1457188

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

724630

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33450

American (AMR)

AF:

0.000158

AC:

AN:

44382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25950

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39582

South Asian (SAS)

AF:

0.00

AC:

AN:

85396

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51688

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000198

AC:

AN:

1110842

Other (OTH)

AF:

0.0000166

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.0000394

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41452

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

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:

0.0000564

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000250

AC:

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

0.088

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.034

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.58

M_CAP

Benign

0.021

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.91

PhyloP100

0.65

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.32

REVEL

Benign

0.020

Sift

Benign

1.0

Sift4G

Benign

0.42

Polyphen

0.36

Vest4

0.44

MutPred

0.39

Loss of disorder (P = 0.0812)

MVP

0.20

MPC

0.12

ClinPred

0.021

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.28

Mutation Taster

=94/6

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