9-136669940-G-A

Variant names:

• chr9-136669940-G-A
• rs61736886
• NM_016215.5:c.340G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016215.5(EGFL7):​c.340G>A​(p.Gly114Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000554 in 1,605,494 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.0028 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (3 hom.)
• Consequence: EGFL7 NM_016215.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.49

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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01774624).
• BP6: Variant 9-136669940-G-A is Benign according to our data. Variant chr9-136669940-G-A is described in ClinVar as [Benign]. Clinvar id is 716928.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL7	NM_016215.5	c.340G>A	p.Gly114Arg	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.340G>A	p.Gly114Arg	missense_variant	Exon 7 of 11	1	NM_016215.5	ENSP00000307843.7

Frequencies

GnomAD3 genomes AF: 0.00276 AC: 420 AN: 152248 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00984

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

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: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000678 AC: 159 AN: 234344 AF XY: 0.000492

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.000210

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000478

Gnomad OTH exome AF: 0.000176

GnomAD4 exome AF: 0.000322 AC: 468 AN: 1453128 Hom.: 3 Cov.: 31 AF XY: 0.000253 AC XY: 183 AN XY: 722332

Gnomad4 AFR exome AF: 0.0117 AC: 388 AN: 33286

Gnomad4 AMR exome AF: 0.000205 AC: 9 AN: 43960

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25906

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39342

Gnomad4 SAS exome AF: 0.0000352 AC: 3 AN: 85136

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 51378

Gnomad4 NFE exome AF: 0.0000262 AC: 29 AN: 1108698

Gnomad4 Remaining exome AF: 0.000617 AC: 37 AN: 59954

GnomAD4 genome AF: 0.00277 AC: 422 AN: 152366 Hom.: 2 Cov.: 33 AF XY: 0.00281 AC XY: 209 AN XY: 74508

Gnomad4 AFR AF: 0.00986 AC: 0.00985814 AN: 0.00985814

Gnomad4 AMR AF: 0.000392 AC: 0.00039185 AN: 0.00039185

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: 0.0000294 AC: 0.0000293971 AN: 0.0000293971

Gnomad4 OTH AF: 0.00189 AC: 0.00189215 AN: 0.00189215

Alfa AF: 0.00147 Hom.: 1

Bravo AF: 0.00320

ESP6500AA AF: 0.0103 AC: 45

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000881 AC: 106

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.51	D;D;D;D
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	.;D;.;.
MetaRNN	Benign	0.018	T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Uncertain	2.3	M;M;M;M
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-7.0	D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.035	D;D;D;D
Sift4G	Uncertain	0.050	T;T;T;T
Polyphen		1.0	D;D;D;D
Vest4		0.63
MutPred		0.36		Gain of phosphorylation at S116 (P = 0.1138);Gain of phosphorylation at S116 (P = 0.1138);Gain of phosphorylation at S116 (P = 0.1138);Gain of phosphorylation at S116 (P = 0.1138);
MVP		0.73
MPC		0.57
ClinPred		0.11	T
GERP RS		4.8
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.31
gMVP		0.68
Mutation Taster		=46/54	disease causing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61736886; hg19: chr9-139564392;