rs11789185

chr9-127845239-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENG	NM_001114753.3	c.68-1994A>C		intron_variant		ENST00000373203.9
ENG	NM_000118.4	c.68-1994A>C		intron_variant
ENG	NM_001278138.2	c.-480+1704A>C		intron_variant
ENG	NM_001406715.1	c.68-1994A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENG	ENST00000373203.9	c.68-1994A>C		intron_variant		1	NM_001114753.3	P2
ENG	ENST00000344849.4	c.68-1994A>C		intron_variant		1		A2
ENG	ENST00000480266.6	c.-480+1704A>C		intron_variant		2

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

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.878

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.914

Gnomad4 NFE AF: 0.908

Gnomad4 OTH AF: 0.783

Alfa AF: 0.884 Hom.: 77052

Bravo AF: 0.747

Asia WGS AF: 0.872 AC: 3031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	8.3
Dann	Benign	0.62

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: rs11789185; hg19: chr9-130607518;