rs370943570

Variant names:

• chr9-127816025-G-A
• rs370943570
• NM_001114753.3:c.1770C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-127816025-G-A
• chr9-127816025-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001114753.3(ENG):​c.1770C>T​(p.Pro590Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000522 in 1,610,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: ENG NM_001114753.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.460

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]

ENSG00000225032 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 9-127816025-G-A is Benign according to our data. Variant chr9-127816025-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 528075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.46 with no splicing effect.
• BS2: High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENG	NM_001114753.3	c.1770C>T	p.Pro590Pro	synonymous_variant	Exon 14 of 15	ENST00000373203.9	NP_001108225.1
ENG	NM_000118.4	c.1770C>T	p.Pro590Pro	synonymous_variant	Exon 14 of 14		NP_000109.1
ENG	NM_001278138.2	c.1224C>T	p.Pro408Pro	synonymous_variant	Exon 14 of 15		NP_001265067.1
LOC102723566	NR_136302.1	n.-41G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENG	ENST00000373203.9	c.1770C>T	p.Pro590Pro	synonymous_variant	Exon 14 of 15	1	NM_001114753.3	ENSP00000362299.4
ENG	ENST00000344849.4	c.1770C>T	p.Pro590Pro	synonymous_variant	Exon 14 of 14	1		ENSP00000341917.3
ENG	ENST00000480266.6	c.1224C>T	p.Pro408Pro	synonymous_variant	Exon 14 of 15	2		ENSP00000479015.1
ENSG00000225032	ENST00000439298.5	n.-41G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000493 AC: 12 AN: 243256 Hom.: 0 AF XY: 0.0000303 AC XY: 4 AN XY: 132068

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000177

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000546

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000494 AC: 72 AN: 1458380 Hom.: 0 Cov.: 31 AF XY: 0.0000427 AC XY: 31 AN XY: 725180

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000225

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.0000830

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74372

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000386 Hom.: 0

Bravo AF: 0.000102

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hereditary hemorrhagic telangiectasia Benign:1

Oct 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

Dec 07, 2020

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.88

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: rs370943570; hg19: chr9-130578304;