rs4837192

Variant names:

• chr9-127852633-G-A
• rs4837192
• NM_001114753.3:c.67+1656C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-127852633-G-A
• chr9-127852633-G-C
• chr9-127852633-G-T

Variant summary

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

The NM_001114753.3(ENG):​c.67+1656C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 151,870 control chromosomes in the GnomAD database, including 46,211 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 0.76 (46211 hom., cov: 29)
• Consequence: ENG NM_001114753.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.417
• Publications: 8 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: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• hereditary hemorrhagic telangiectasia

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

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LOC124902279 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.87 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.67+1656C>T		intron	N/A	NP_001108225.1	P17813-1
	ENG	NM_000118.4		c.67+1656C>T		intron	N/A	NP_000109.1	Q5T9B9
	ENG	NM_001406715.1		c.67+1656C>T		intron	N/A	NP_001393644.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENG	ENST00000373203.9	TSL:1 MANE Select	c.67+1656C>T		intron	N/A	ENSP00000362299.4	P17813-1
	ENG	ENST00000344849.5	TSL:1	c.67+1656C>T		intron	N/A	ENSP00000341917.3	P17813-2
	ENG	ENST00000714047.1		c.67+1656C>T		intron	N/A	ENSP00000519338.1	A0AAQ5BHC4

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115599 AN: 151752 Hom.: 46209 Cov.: 29

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.913

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.761 AC: 115645 AN: 151870 Hom.: 46211 Cov.: 29 AF XY: 0.766 AC XY: 56824 AN XY: 74226

African (AFR) AF: 0.496 AC: 20479 AN: 41302

American (AMR) AF: 0.788 AC: 12022 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3004 AN: 3466

East Asian (EAS) AF: 0.811 AC: 4192 AN: 5168

South Asian (SAS) AF: 0.890 AC: 4266 AN: 4792

European-Finnish (FIN) AF: 0.913 AC: 9666 AN: 10592

Middle Eastern (MID) AF: 0.784 AC: 229 AN: 292

European-Non Finnish (NFE) AF: 0.876 AC: 59556 AN: 67982

Other (OTH) AF: 0.773 AC: 1635 AN: 2114

Alfa AF: 0.845 Hom.: 85684

Bravo AF: 0.740

Asia WGS AF: 0.825 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.70
PhyloP100		-0.42
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: rs4837192; hg19: chr9-130614912;