9-136671948-C-G

Variant names:

• chr9-136671948-C-G
• rs897682448
• NM_016215.5:c.659C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_016215.5(EGFL7):​c.659C>G​(p.Pro220Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P220L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFL7 NM_016215.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.57
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.87

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.659C>G	p.Pro220Arg	missense	Exon 10 of 11	NP_057299.1	Q9UHF1
	EGFL7	NM_201446.3		c.659C>G	p.Pro220Arg	missense	Exon 8 of 9	NP_958854.1	Q9UHF1
	EGFL7	NR_045110.2		n.985C>G		non_coding_transcript_exon	Exon 9 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL7	ENST00000308874.12	TSL:1 MANE Select	c.659C>G	p.Pro220Arg	missense	Exon 10 of 11	ENSP00000307843.7	Q9UHF1
	EGFL7	ENST00000371698.3	TSL:1	c.659C>G	p.Pro220Arg	missense	Exon 8 of 9	ENSP00000360763.3	Q9UHF1
	EGFL7	ENST00000406555.7	TSL:1	c.659C>G	p.Pro220Arg	missense	Exon 9 of 10	ENSP00000385639.3	Q9UHF1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.61	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.62
Sift	Benign	0.87	T
Sift4G	Uncertain	0.052	T
Polyphen		1.0	D
Vest4		0.77
MVP		0.97
MPC		0.53
ClinPred		0.99	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.34
gMVP		0.58
Mutation Taster		=40/60	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs897682448; hg19: chr9-139566400;