9-136670512-C-G

Variant names:

• chr9-136670512-C-G
• rs78242242
• NM_016215.5:c.571+182C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016215.5(EGFL7):​c.571+182C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 708,480 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: EGFL7 NM_016215.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL7	NM_016215.5	c.571+182C>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.571+182C>G		intron_variant	Intron 8 of 10	1	NM_016215.5	ENSP00000307843.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000423 AC: 3 AN: 708480 Hom.: 0 Cov.: 9 AF XY: 0.00000266 AC XY: 1 AN XY: 375252

African (AFR) AF: 0.00 AC: 0 AN: 18478

American (AMR) AF: 0.00 AC: 0 AN: 36182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20850

East Asian (EAS) AF: 0.00 AC: 0 AN: 34114

South Asian (SAS) AF: 0.00 AC: 0 AN: 66604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3666

European-Non Finnish (NFE) AF: 0.00000675 AC: 3 AN: 444508

Other (OTH) AF: 0.00 AC: 0 AN: 35180

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.49
PhyloP100		-1.4

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

Other links and lift over

dbSNP: rs78242242; hg19: chr9-139564964;