Variant 9-136672058-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016215.5(EGFL7):c.769A>G(p.Ile257Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,394,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

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: 2.72

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL7	NM_016215.5 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	10/11	ENST00000308874.12	NP_057299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
EGFL7	ENST00000308874.12 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	10/11	1	NM_016215.5	ENSP00000307843	P1
EGFL7	ENST00000371698.3 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	8/9	1		ENSP00000360763	P1
EGFL7	ENST00000406555.7 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	9/10	1		ENSP00000385639	P1
EGFL7	ENST00000371699.5 linkuse as main transcript	c.769A>G	p.Ile257Val	missense_variant	9/10	2		ENSP00000360764	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000264

AC:

AN:

151608

Hom.:

AF XY:

0.0000247

AC XY:

AN XY:

81074

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000162

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1394252

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

688038

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Jul 20, 2021

The c.769A>G (p.I257V) alteration is located in exon 10 (coding exon 7) of the EGFL7 gene. This alteration results from a A to G substitution at nucleotide position 769, causing the isoleucine (I) at amino acid position 257 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

0.18

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.066

T;T;T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.48

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.76

.;T;.;.

M_CAP

Benign

0.043

MetaRNN

Benign

0.080

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.77

N;N;N;N

MutationTaster

Benign

0.75

D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.19

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

0.058

B;B;B;B

Vest4

0.32

MutPred

0.35

Gain of phosphorylation at S258 (P = 0.2152);Gain of phosphorylation at S258 (P = 0.2152);Gain of phosphorylation at S258 (P = 0.2152);Gain of phosphorylation at S258 (P = 0.2152);

MVP

0.42

MPC

0.093

ClinPred

0.030

GERP RS

1.6

Varity_R

0.013

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.35

Position offset: -1

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