9-127817320-C-T

Position:

chr9-127817320-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001114753.3(ENG):c.1687-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 997,594 control chromosomes in the GnomAD database, including 69,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8371 hom., cov: 32)

Exomes 𝑓: 0.37 ( 61197 hom. )

Consequence

ENG
NM_001114753.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.429

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-127817320-C-T is Benign according to our data. Variant chr9-127817320-C-T is described in ClinVar as [Benign]. Clinvar id is 439656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
ENG	NM_001114753.3 linkuse as main transcript	c.1687-117G>A	intron_variant		ENST00000373203.9	NP_001108225.1
LOC102723566	NR_136302.1 linkuse as main transcript	n.1255C>T	non_coding_transcript_exon_variant	1/6
ENG	NM_000118.4 linkuse as main transcript	c.1687-117G>A	intron_variant			NP_000109.1
ENG	NM_001278138.2 linkuse as main transcript	c.1141-117G>A	intron_variant			NP_001265067.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENG	ENST00000373203.9 linkuse as main transcript	c.1687-117G>A	intron_variant		1	NM_001114753.3	ENSP00000362299	P2	P17813-1
ENG	ENST00000344849.4 linkuse as main transcript	c.1687-117G>A	intron_variant		1		ENSP00000341917	A2	P17813-2
	ENST00000439298.5 linkuse as main transcript	n.1255C>T	non_coding_transcript_exon_variant	1/6	2
ENG	ENST00000480266.6 linkuse as main transcript	c.1141-117G>A	intron_variant		2		ENSP00000479015

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45148

AN:

151950

Hom.:

8378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0762

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.326

GnomAD4 exome

AF:

0.370

AC:

312816

AN:

845526

Hom.:

61197

Cov.:

AF XY:

0.368

AC XY:

161937

AN XY:

439578

show subpopulations

Gnomad4 AFR exome

AF:

0.0686

Gnomad4 AMR exome

AF:

0.415

Gnomad4 ASJ exome

AF:

0.336

Gnomad4 EAS exome

AF:

0.602

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.315

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.353

GnomAD4 genome

AF:

0.297

AC:

45143

AN:

152068

Hom.:

8371

Cov.:

AF XY:

0.295

AC XY:

21927

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0760

Gnomad4 AMR

AF:

0.378

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.583

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.384

Gnomad4 OTH

AF:

0.325

Alfa

AF:

0.343

Hom.:

2310

Bravo

AF:

0.298

Asia WGS

AF:

0.376

AC:

1309

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Telangiectasia, hereditary hemorrhagic, type 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Apr 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.0

DANN

Benign

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over