dbSNP rs4636297: EGFL7:c.572-252A>G (chr9-136670698-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016215.5(EGFL7):c.572-252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 769,306 control chromosomes in the GnomAD database, including 169,328 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.65 ( 32341 hom., cov: 36)

Exomes 𝑓: 0.66 ( 136987 hom. )

Consequence

EGFL7
NM_016215.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.388

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:

MIR126 (HGNC:31508): (microRNA 126) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR126 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL7	NM_016215.5 link	c.572-252A>G		intron_variant	Intron 8 of 10	ENST00000308874.12	NP_057299.1	Q9UHF1A0A024R8F5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL7	ENST00000308874.12 link	c.572-252A>G		intron_variant	Intron 8 of 10	1	NM_016215.5	ENSP00000307843.7		Q9UHF1

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98742

AN:

152058

Hom.:

32328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.581

Gnomad EAS

AF:

0.843

Gnomad SAS

AF:

0.727

Gnomad FIN

AF:

0.713

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.641

Gnomad OTH

AF:

0.594

GnomAD3 exomes

AF:

0.667

AC:

162894

AN:

244366

Hom.:

54782

AF XY:

0.666

AC XY:

88593

AN XY:

132936

show subpopulations

Gnomad AFR exome

AF:

0.632

Gnomad AMR exome

AF:

0.638

Gnomad ASJ exome

AF:

0.597

Gnomad EAS exome

AF:

0.863

Gnomad SAS exome

AF:

0.730

Gnomad FIN exome

AF:

0.702

Gnomad NFE exome

AF:

0.631

Gnomad OTH exome

AF:

0.636

GnomAD4 exome

AF:

0.662

AC:

408710

AN:

617128

Hom.:

136987

Cov.:

AF XY:

0.663

AC XY:

222569

AN XY:

335644

show subpopulations

Gnomad4 AFR exome

AF:

0.630

Gnomad4 AMR exome

AF:

0.636

Gnomad4 ASJ exome

AF:

0.596

Gnomad4 EAS exome

AF:

0.867

Gnomad4 SAS exome

AF:

0.729

Gnomad4 FIN exome

AF:

0.700

Gnomad4 NFE exome

AF:

0.634

Gnomad4 OTH exome

AF:

0.643

GnomAD4 genome

AF:

0.649

AC:

98808

AN:

152178

Hom.:

32341

Cov.:

AF XY:

0.655

AC XY:

48713

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.632

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.581

Gnomad4 EAS

AF:

0.843

Gnomad4 SAS

AF:

0.726

Gnomad4 FIN

AF:

0.713

Gnomad4 NFE

AF:

0.641

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.640

Hom.:

8826

Bravo

AF:

0.637

Asia WGS

AF:

0.748

AC:

2599

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.0

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over