NM_016215.5:c.572-252A>G

Variant names:

• chr9-136670698-A-G
• rs4636297
• NM_016215.5:c.572-252A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 54 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.572-252A>G		intron_variant	Intron 8 of 10	ENST00000308874.12	NP_057299.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98742 AN: 152058 Hom.: 32328 Cov.: 36

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

GnomAD2 exomes AF: 0.667 AC: 162894 AN: 244366 AF XY: 0.666

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 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.: 4 AF XY: 0.663 AC XY: 222569 AN XY: 335644

African (AFR) AF: 0.630 AC: 11017 AN: 17492

American (AMR) AF: 0.636 AC: 27356 AN: 43000

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 12371 AN: 20768

East Asian (EAS) AF: 0.867 AC: 30774 AN: 35502

South Asian (SAS) AF: 0.729 AC: 49969 AN: 68524

European-Finnish (FIN) AF: 0.700 AC: 35730 AN: 51044

Middle Eastern (MID) AF: 0.568 AC: 2327 AN: 4094

European-Non Finnish (NFE) AF: 0.634 AC: 218236 AN: 344132

Other (OTH) AF: 0.643 AC: 20930 AN: 32572

GnomAD4 genome AF: 0.649 AC: 98808 AN: 152178 Hom.: 32341 Cov.: 36 AF XY: 0.655 AC XY: 48713 AN XY: 74404

African (AFR) AF: 0.632 AC: 26242 AN: 41512

American (AMR) AF: 0.627 AC: 9587 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2014 AN: 3468

East Asian (EAS) AF: 0.843 AC: 4347 AN: 5156

South Asian (SAS) AF: 0.726 AC: 3508 AN: 4832

European-Finnish (FIN) AF: 0.713 AC: 7570 AN: 10610

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.641 AC: 43576 AN: 67976

Other (OTH) AF: 0.595 AC: 1260 AN: 2116

Alfa AF: 0.636 Hom.: 11058

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
PhyloP100		-0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4636297; hg19: chr9-139565150; COSMIC: COSV58247283; COSMIC: COSV58247283;