9-136669988-C-T

Variant names:

• chr9-136669988-C-T
• rs139118330
• NM_016215.5:c.388C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016215.5(EGFL7):​c.388C>T​(p.Arg130Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000807 in 1,599,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000084 (0 hom.)
• Consequence: EGFL7 NM_016215.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.172

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20679641).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL7	NM_016215.5	c.388C>T	p.Arg130Trp	missense_variant	Exon 7 of 11	ENST00000308874.12	NP_057299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL7	ENST00000308874.12	c.388C>T	p.Arg130Trp	missense_variant	Exon 7 of 11	1	NM_016215.5	ENSP00000307843.7

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000515 AC: 12 AN: 232972 AF XY: 0.0000392

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000300

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000865

Gnomad OTH exome AF: 0.000177

GnomAD4 exome AF: 0.0000836 AC: 121 AN: 1446776 Hom.: 0 Cov.: 31 AF XY: 0.0000724 AC XY: 52 AN XY: 717892

Gnomad4 AFR exome AF: 0.0000301 AC: 1 AN: 33270

Gnomad4 AMR exome AF: 0.000137 AC: 6 AN: 43848

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25592

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39372

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 84966

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 50756

Gnomad4 NFE exome AF: 0.000101 AC: 111 AN: 1103636

Gnomad4 Remaining exome AF: 0.0000503 AC: 3 AN: 59674

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152306 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74474

Gnomad4 AFR AF: 0.00 AC: 0 AN: 0

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000118 AC: 0.000117616 AN: 0.000117616

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.0000305 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000832 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.388C>T (p.R130W) alteration is located in exon 7 (coding exon 4) of the EGFL7 gene. This alteration results from a C to T substitution at nucleotide position 388, causing the arginine (R) at amino acid position 130 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T;T;T;T
Eigen	Benign	0.058
Eigen_PC	Benign	-0.024
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.92	.;D;.;.
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.046	D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;D
Polyphen		0.99	D;D;D;D
Vest4		0.30
MVP		0.35
MPC		0.38
ClinPred		0.18	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.41
Mutation Taster		=85/15	polymorphism

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

Publications

LitVar

Other links and lift over

dbSNP: rs139118330; hg19: chr9-139564440; COSMIC: COSV58248342; COSMIC: COSV58248342;