rs11789185

Variant names:

• chr9-127845239-T-G
• rs11789185
• NM_001114753.3:c.68-1994A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001114753.3(ENG):​c.68-1994A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 152,190 control chromosomes in the GnomAD database, including 48,149 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (48149 hom., cov: 33)
• Consequence: ENG NM_001114753.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 9 publications found

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]

ENG Gene-Disease associations (from GenCC):

• telangiectasia, hereditary hemorrhagic, type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, ClinGen
• hereditary hemorrhagic telangiectasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• juvenile polyposis syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114753.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENG	NM_001114753.3	MANE Select	c.68-1994A>C		intron	N/A	NP_001108225.1
	ENG	NM_000118.4		c.68-1994A>C		intron	N/A	NP_000109.1
	ENG	NM_001278138.2		c.-480+1704A>C		intron	N/A	NP_001265067.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENG	ENST00000373203.9	TSL:1 MANE Select	c.68-1994A>C		intron	N/A	ENSP00000362299.4
	ENG	ENST00000344849.5	TSL:1	c.68-1994A>C		intron	N/A	ENSP00000341917.3
	ENG	ENST00000714047.1		c.68-1994A>C		intron	N/A	ENSP00000519338.1

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116510 AN: 152072 Hom.: 48141 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.878

Gnomad FIN AF: 0.914

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.766 AC: 116548 AN: 152190 Hom.: 48149 Cov.: 33 AF XY: 0.769 AC XY: 57234 AN XY: 74416

African (AFR) AF: 0.425 AC: 17610 AN: 41472

American (AMR) AF: 0.843 AC: 12897 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3047 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4822 AN: 5168

South Asian (SAS) AF: 0.878 AC: 4237 AN: 4826

European-Finnish (FIN) AF: 0.914 AC: 9701 AN: 10612

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61735 AN: 68024

Other (OTH) AF: 0.783 AC: 1650 AN: 2106

Alfa AF: 0.861 Hom.: 101845

Bravo AF: 0.747

Asia WGS AF: 0.872 AC: 3031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.3
DANN	Benign	0.62
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11789185; hg19: chr9-130607518;