chr9-127815213-CAGTT-C

Position:

• chr9-127815213-CAGTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001114753.3(ENG):​c.*465_*468del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0706 in 156,490 control chromosomes in the GnomAD database, including 438 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.071 (427 hom., cov: 32)
  • Exomes 𝑓: 0.058 (11 hom.)
• Consequence: ENG NM_001114753.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.815

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 -10 ACMG points.

• BP6: Variant 9-127815213-CAGTT-C is Benign according to our data. Variant chr9-127815213-CAGTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 365078.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-127815213-CAGTT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENG	NM_001114753.3	c.*465_*468del		3_prime_UTR_variant	15/15	ENST00000373203.9
ENG	NM_000118.4	c.*700_*703del		3_prime_UTR_variant	14/14
ENG	NM_001278138.2	c.*465_*468del		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENG	ENST00000373203.9	c.*465_*468del		3_prime_UTR_variant	15/15	1	NM_001114753.3	P2
ENG	ENST00000344849.4	c.*700_*703del		3_prime_UTR_variant	14/14	1		A2
ENG	ENST00000480266.6	c.*465_*468del		3_prime_UTR_variant	15/15	2

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10807 AN: 152182 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0671

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0822

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0674

GnomAD4 exome AF: 0.0582 AC: 244 AN: 4190 Hom.: 11 AF XY: 0.0619 AC XY: 135 AN XY: 2180

Gnomad4 AFR exome AF: 0.0132

Gnomad4 AMR exome AF: 0.0289

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0164

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.0833

Gnomad4 NFE exome AF: 0.0631

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0709 AC: 10802 AN: 152300 Hom.: 427 Cov.: 32 AF XY: 0.0735 AC XY: 5471 AN XY: 74486

Gnomad4 AFR AF: 0.0480

Gnomad4 AMR AF: 0.0671

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0822

Gnomad4 NFE AF: 0.0796

Gnomad4 OTH AF: 0.0681

Alfa AF: 0.0309 Hom.: 19

Bravo AF: 0.0637

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Telangiectasia, hereditary hemorrhagic, type 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs41514846; hg19: chr9-130577492;