rs4837192

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124902279 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENG	NM_001114753.3	c.67+1656C>T		intron_variant		ENST00000373203.9	NP_001108225.1
ENG	NM_000118.4	c.67+1656C>T		intron_variant			NP_000109.1
ENG	NM_001406715.1	c.67+1656C>T		intron_variant			NP_001393644.1
LOC124902279	XR_007061800.1	n.91-52G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENG	ENST00000373203.9	c.67+1656C>T		intron_variant		1	NM_001114753.3	ENSP00000362299.4
ENG	ENST00000344849.4	c.67+1656C>T		intron_variant		1		ENSP00000341917.3

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

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.890

Gnomad4 FIN AF: 0.913

Gnomad4 NFE AF: 0.876

Gnomad4 OTH AF: 0.773

Alfa AF: 0.857 Hom.: 67885

Bravo AF: 0.740

Asia WGS AF: 0.825 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.70

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: rs4837192; hg19: chr9-130614912;