rs115450389

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001114753.3(ENG):c.1452C>T(p.Ser484Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000899 in 1,613,796 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 3 hom. )

Consequence

ENG
NM_001114753.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.29

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

telangiectasia, hereditary hemorrhagic, type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
hereditary hemorrhagic telangiectasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
juvenile polyposis syndrome
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENG links:

ENSG00000225032 (HGNC:):

ENSG00000225032 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 9-127818354-G-A is Benign according to our data. Variant chr9-127818354-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255142.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00295 (449/152334) while in subpopulation AFR AF = 0.00873 (363/41562). AF 95% confidence interval is 0.00799. There are 3 homozygotes in GnomAd4. There are 205 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 449 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001114753.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENG	NM_001114753.3	MANE Select	c.1452C>T	p.Ser484Ser	synonymous	Exon 12 of 15	NP_001108225.1	P17813-1
ENG	NM_000118.4		c.1452C>T	p.Ser484Ser	synonymous	Exon 12 of 14	NP_000109.1	Q5T9B9
ENG	NM_001278138.2		c.906C>T	p.Ser302Ser	synonymous	Exon 12 of 15	NP_001265067.1	F5GX88

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENG	ENST00000373203.9	TSL:1 MANE Select	c.1452C>T	p.Ser484Ser	synonymous	Exon 12 of 15	ENSP00000362299.4	P17813-1
ENG	ENST00000344849.5	TSL:1	c.1452C>T	p.Ser484Ser	synonymous	Exon 12 of 14	ENSP00000341917.3	P17813-2
ENG	ENST00000714047.1		c.1452C>T	p.Ser484Ser	synonymous	Exon 12 of 15	ENSP00000519338.1	A0AAQ5BHC4

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

446

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00866

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00112

AC:

279

AN:

248912

AF XY:

0.000890

show subpopulations

Gnomad AFR exome

AF:

0.00896

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000420

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.000686

AC:

1002

AN:

1461462

Hom.:

Cov.:

AF XY:

0.000640

AC XY:

465

AN XY:

727002

show subpopulations

African (AFR)

AF:

0.00821

AC:

275

AN:

33480

American (AMR)

AF:

0.00188

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53030

Middle Eastern (MID)

AF:

0.00364

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000463

AC:

515

AN:

1111996

Other (OTH)

AF:

0.00154

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

142

212

283

354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00295

AC:

449

AN:

152334

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.00873

AC:

363

AN:

41562

American (AMR)

AF:

0.00209

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68028

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00143

Hom.:

Bravo

AF:

0.00319

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Telangiectasia, hereditary hemorrhagic, type 1 (2)

Cardiovascular phenotype (1)

Hereditary hemorrhagic telangiectasia (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.2

(source)

DANN

Benign

0.72

PhyloP100

-1.3

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over