rs201768056

chr9-127816033-C-Gchr9-127816033-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001114753.3(ENG):c.1762G>C(p.Val588Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. V588I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENG NM_001114753.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.485

Genes affected

ENG (HGNC:3349): (endoglin) This gene encodes a homodimeric transmembrane protein which is a major glycoprotein of the vascular endothelium. This protein is a component of the transforming growth factor beta receptor complex and it binds to the beta1 and beta3 peptides with high affinity. Mutations in this gene cause hereditary hemorrhagic telangiectasia, also known as Osler-Rendu-Weber syndrome 1, an autosomal dominant multisystemic vascular dysplasia. This gene may also be involved in preeclampsia and several types of cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09086117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENG	NM_001114753.3	c.1762G>C	p.Val588Leu	missense_variant	14/15	ENST00000373203.9
ENG	NM_000118.4	c.1762G>C	p.Val588Leu	missense_variant	14/14
ENG	NM_001278138.2	c.1216G>C	p.Val406Leu	missense_variant	14/15
LOC102723566	NR_136302.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENG	ENST00000373203.9	c.1762G>C	p.Val588Leu	missense_variant	14/15	1	NM_001114753.3	P2
ENG	ENST00000344849.4	c.1762G>C	p.Val588Leu	missense_variant	14/14	1		A2
ENG	ENST00000480266.6	c.1216G>C	p.Val406Leu	missense_variant	14/15	2
	ENST00000439298.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458058 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725036

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	10
Dann	Benign	0.83
DEOGEN2	Uncertain	0.42	T;T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L
MutationTaster	Benign	0.85	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N;.;N
REVEL	Benign	0.018
Sift	Benign	0.15	T;.;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.0090	B;.;.
Vest4		0.26
MutPred		0.24		Loss of methylation at K585 (P = 0.0682);.;Loss of methylation at K585 (P = 0.0682);
MVP		0.41
MPC		0.21
ClinPred		0.062	T
GERP RS		-0.0068
Varity_R		0.098
gMVP		0.63

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: rs201768056; hg19: chr9-130578312;