9-127816125-A-G

Variant names:

Variant summary

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

The NM_001114753.3(ENG):c.1742-72T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,549,808 control chromosomes in the GnomAD database, including 156,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15457 hom., cov: 33)

Exomes 𝑓: 0.45 ( 140843 hom. )

Consequence

ENG
NM_001114753.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.696

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:

ENSG00000225032 (HGNC:):

ENSG00000225032 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=-0.91).

BP6

Variant 9-127816125-A-G is Benign according to our data. Variant chr9-127816125-A-G is described in ClinVar as [Benign]. Clinvar id is 672484.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ENG	NM_001114753.3 link	c.1742-72T>C	intron_variant	Intron 13 of 14	ENST00000373203.9	NP_001108225.1	P17813-1Q96CG0A0A024R878
ENG	NM_000118.4 link	c.1742-72T>C	intron_variant	Intron 13 of 13		NP_000109.1	P17813-2Q5T9B9
ENG	NM_001278138.2 link	c.1196-72T>C	intron_variant	Intron 13 of 14		NP_001265067.1	P17813Q96CG0F5GX88B7Z6Y5
LOC102723566	NR_136302.1 link	n.60A>G	non_coding_transcript_exon_variant	Exon 1 of 6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENG	ENST00000373203.9 link	c.1742-72T>C	intron_variant	Intron 13 of 14	1	NM_001114753.3	ENSP00000362299.4	P17813-1
ENG	ENST00000344849.4 link	c.1742-72T>C	intron_variant	Intron 13 of 13	1		ENSP00000341917.3	P17813-2
ENG	ENST00000480266.6 link	c.1196-72T>C	intron_variant	Intron 13 of 14	2		ENSP00000479015.1	F5GX88
ENSG00000225032	ENST00000439298.5 link	n.60A>G	non_coding_transcript_exon_variant	Exon 1 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

68111

AN:

151896

Hom.:

15444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.474

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.693

Gnomad SAS

AF:

0.392

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.446

AC:

622841

AN:

1397794

Hom.:

140843

Cov.:

AF XY:

0.443

AC XY:

306689

AN XY:

691566

show subpopulations

Gnomad4 AFR exome

AF:

0.431

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.433

Gnomad4 EAS exome

AF:

0.688

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.382

Gnomad4 NFE exome

AF:

0.444

Gnomad4 OTH exome

AF:

0.448

GnomAD4 genome

AF:

0.448

AC:

68168

AN:

152014

Hom.:

15457

Cov.:

AF XY:

0.446

AC XY:

33110

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.440

Gnomad4 AMR

AF:

0.473

Gnomad4 ASJ

AF:

0.451

Gnomad4 EAS

AF:

0.693

Gnomad4 SAS

AF:

0.393

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.442

Gnomad4 OTH

AF:

0.469

Alfa

AF:

0.434

Hom.:

12833

Bravo

AF:

0.461

Asia WGS

AF:

0.518

AC:

1804

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.8

DANN

Benign

0.24

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