Variant chr9-136669935-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_016215.5(EGFL7):c.335G>A(p.Arg112Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,604,008 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 43 hom. )

Consequence

EGFL7
NM_016215.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.881

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009594649).

BP6

Variant 9-136669935-G-A is Benign according to our data. Variant chr9-136669935-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 774468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL7	NM_016215.5 linkuse as main transcript	c.335G>A	p.Arg112Gln	missense_variant	7/11	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.335G>A	p.Arg112Gln	missense_variant	7/11	1	NM_016215.5	ENSP00000307843	P1

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

636

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00701

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00382

AC:

887

AN:

232274

Hom.:

AF XY:

0.00384

AC XY:

488

AN XY:

126944

show subpopulations

Gnomad AFR exome

AF:

0.00147

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.000105

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.00169

Gnomad FIN exome

AF:

0.00118

Gnomad NFE exome

AF:

0.00662

Gnomad OTH exome

AF:

0.00514

GnomAD4 exome

AF:

0.00606

AC:

8803

AN:

1451656

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

4335

AN XY:

721438

show subpopulations

Gnomad4 AFR exome

AF:

0.00129

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.000271

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00203

Gnomad4 FIN exome

AF:

0.00121

Gnomad4 NFE exome

AF:

0.00730

Gnomad4 OTH exome

AF:

0.00534

GnomAD4 genome

AF:

0.00417

AC:

636

AN:

152352

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00701

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00551

Hom.:

Bravo

AF:

0.00427

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00207

AC:

ESP6500EA

AF:

0.00772

AC:

ExAC

AF:

0.00373

AC:

448

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	EGFL7: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.031

T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.84

.;T;.;.

MetaRNN

Benign

0.0096

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.94

N;N;N;N

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

1.5

N;N;N;N

REVEL

Benign

0.023

Sift

Benign

0.42

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0060

B;B;B;B

Vest4

0.10

MVP

0.51

MPC

0.12

ClinPred

0.0025

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.013

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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