rs11792480

Variant names:

• chr9-127835846-G-A
• rs11792480
• NM_001114753.3:c.220-6019C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-127835846-G-A
• chr9-127835846-G-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.220-6019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,036 control chromosomes in the GnomAD database, including 5,828 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 0.24 (5828 hom., cov: 31)
• Consequence: ENG NM_001114753.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 16 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENG	NM_001114753.3	MANE Select	c.220-6019C>T		intron	N/A	NP_001108225.1	P17813-1
	ENG	NM_000118.4		c.220-6019C>T		intron	N/A	NP_000109.1	Q5T9B9
	ENG	NM_001278138.2		c.-327-6019C>T		intron	N/A	NP_001265067.1	F5GX88

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENG	ENST00000373203.9	TSL:1 MANE Select	c.220-6019C>T		intron	N/A	ENSP00000362299.4	P17813-1
	ENG	ENST00000344849.5	TSL:1	c.220-6019C>T		intron	N/A	ENSP00000341917.3	P17813-2
	ENG	ENST00000714047.1		c.220-6019C>T		intron	N/A	ENSP00000519338.1	A0AAQ5BHC4

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36912 AN: 151916 Hom.: 5826 Cov.: 31

Gnomad AFR AF: 0.0665

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.00560

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.243 AC: 36911 AN: 152036 Hom.: 5828 Cov.: 31 AF XY: 0.236 AC XY: 17539 AN XY: 74304

African (AFR) AF: 0.0663 AC: 2754 AN: 41538

American (AMR) AF: 0.241 AC: 3685 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1622 AN: 3468

East Asian (EAS) AF: 0.00561 AC: 29 AN: 5170

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4818

European-Finnish (FIN) AF: 0.233 AC: 2464 AN: 10556

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24129 AN: 67910

Other (OTH) AF: 0.273 AC: 576 AN: 2108

Alfa AF: 0.330 Hom.: 17332

Bravo AF: 0.233

Asia WGS AF: 0.113 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.054
DANN	Benign	0.67
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11792480; hg19: chr9-130598125;