Variant chr9-136669668-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10185751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL7	NM_016215.5 linkuse as main transcript	c.260C>T	p.Ala87Val	missense_variant	6/11	ENST00000308874.12	NP_057299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFL7	ENST00000308874.12 linkuse as main transcript	c.260C>T	p.Ala87Val	missense_variant	6/11	1	NM_016215.5	ENSP00000307843	P1

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

GnomAD3 exomes

AF:

0.0000293

AC:

AN:

239018

Hom.:

AF XY:

0.00000767

AC XY:

AN XY:

130418

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000158

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000250

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.260C>T (p.A87V) alteration is located in exon 6 (coding exon 3) of the EGFL7 gene. This alteration results from a C to T substitution at nucleotide position 260, causing the alanine (A) at amino acid position 87 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.034

T;T;T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.58

.;T;.;.

M_CAP

Benign

0.021

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.91

L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.32

N;N;N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.42

T;T;T;T

Polyphen

0.36

B;B;B;B

Vest4

0.44

MutPred

0.39

Loss of disorder (P = 0.0812);Loss of disorder (P = 0.0812);Loss of disorder (P = 0.0812);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

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

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