rs11792480

chr9-127835846-G-Achr9-127835846-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENG	NM_001114753.3	c.220-6019C>T		intron_variant		ENST00000373203.9
ENG	NM_000118.4	c.220-6019C>T		intron_variant
ENG	NM_001278138.2	c.-327-6019C>T		intron_variant
ENG	NM_001406715.1	c.220-6019C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENG	ENST00000373203.9	c.220-6019C>T		intron_variant		1	NM_001114753.3	P2
ENG	ENST00000344849.4	c.220-6019C>T		intron_variant		1		A2
ENG	ENST00000480266.6	c.-327-6019C>T		intron_variant		2

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

Gnomad4 AFR AF: 0.0663

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.00561

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.273

Alfa AF: 0.346 Hom.: 13501

Bravo AF: 0.233

Asia WGS AF: 0.113 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.054
Dann	Benign	0.67

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: rs11792480; hg19: chr9-130598125;