rs1140713

Variant names:

• chr9-136670833-C-T
• rs1140713
• NM_016215.5:c.572-117C>T

Variant summary

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

The NM_016215.5(EGFL7):​c.572-117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 964,086 control chromosomes in the GnomAD database, including 8,051 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 0.12 (1258 hom., cov: 30)
  • Exomes 𝑓: 0.12 (6793 hom.)
• Consequence: EGFL7 NM_016215.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016215.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL7	NM_016215.5	MANE Select	c.572-117C>T		intron	N/A	NP_057299.1	Q9UHF1
	EGFL7	NM_201446.3		c.572-117C>T		intron	N/A	NP_958854.1	Q9UHF1
	EGFL7	NR_045110.2		n.898-117C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL7	ENST00000308874.12	TSL:1 MANE Select	c.572-117C>T		intron	N/A	ENSP00000307843.7	Q9UHF1
	EGFL7	ENST00000371698.3	TSL:1	c.572-117C>T		intron	N/A	ENSP00000360763.3	Q9UHF1
	EGFL7	ENST00000406555.7	TSL:1	c.572-117C>T		intron	N/A	ENSP00000385639.3	Q9UHF1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18942 AN: 151766 Hom.: 1256 Cov.: 30

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.00725

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.167

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.122

GnomAD4 exome AF: 0.123 AC: 99966 AN: 812204 Hom.: 6793 Cov.: 11 AF XY: 0.126 AC XY: 52111 AN XY: 414906

African (AFR) AF: 0.139 AC: 2712 AN: 19492

American (AMR) AF: 0.118 AC: 3507 AN: 29626

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 2612 AN: 18396

East Asian (EAS) AF: 0.00399 AC: 129 AN: 32346

South Asian (SAS) AF: 0.163 AC: 10019 AN: 61336

European-Finnish (FIN) AF: 0.121 AC: 5487 AN: 45346

Middle Eastern (MID) AF: 0.189 AC: 772 AN: 4074

European-Non Finnish (NFE) AF: 0.124 AC: 69943 AN: 563672

Other (OTH) AF: 0.126 AC: 4785 AN: 37916

GnomAD4 genome AF: 0.125 AC: 18979 AN: 151882 Hom.: 1258 Cov.: 30 AF XY: 0.125 AC XY: 9262 AN XY: 74212

African (AFR) AF: 0.135 AC: 5603 AN: 41404

American (AMR) AF: 0.121 AC: 1850 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3466

East Asian (EAS) AF: 0.00727 AC: 37 AN: 5088

South Asian (SAS) AF: 0.170 AC: 818 AN: 4806

European-Finnish (FIN) AF: 0.116 AC: 1225 AN: 10602

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.124 AC: 8430 AN: 67924

Other (OTH) AF: 0.122 AC: 257 AN: 2108

Alfa AF: 0.128 Hom.: 146

Bravo AF: 0.124

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.76
DANN	Benign	0.62
PhyloP100		-2.0
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		1.9
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: rs1140713; hg19: chr9-139565285;