9-136669668-C-T

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

1
18

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]

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
EGFL7NM_016215.5 linkuse as main transcriptc.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
EGFL7ENST00000308874.12 linkuse as main transcriptc.260C>T p.Ala87Val missense_variant 6/111 NM_016215.5 ENSP00000307843 P1

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152204
Hom.:
0
Cov.:
33
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:
7
AN:
239018
Hom.:
0
AF XY:
0.00000767
AC XY:
1
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:
33
AN:
1457188
Hom.:
0
Cov.:
32
AF XY:
0.0000152
AC XY:
11
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:
6
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
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.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000250
AC:
3

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 submitterclinical testingAmbry GeneticsJan 08, 2024The 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
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
16
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
N
LIST_S2
Benign
0.58
.;T;.;.
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.10
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.91
L;L;L;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Uncertain
0.68
T
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
T
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.

Other links and lift over

dbSNP: rs745614827; hg19: chr9-139564120; API