Genetic Variant OBI1-AS1:n.230+5516C>T (chr13-77925434-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000607862.5(OBI1-AS1):n.230+5516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,170 control chromosomes in the GnomAD database, including 884 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 0.10 ( 884 hom., cov: 33)

Consequence

OBI1-AS1
ENST00000607862.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Publications

6 publications found

Variant links:

Genes affected

OBI1-AS1 (HGNC:42700): (OBI1 antisense RNA 1)

OBI1-AS1 links:

EDNRB (HGNC:3180): (endothelin receptor type B) The protein encoded by this gene is a G protein-coupled receptor which activates a phosphatidylinositol-calcium second messenger system. Its ligand, endothelin, consists of a family of three potent vasoactive peptides: ET1, ET2, and ET3. Studies suggest that the multigenic disorder, Hirschsprung disease type 2, is due to mutations in the endothelin receptor type B gene. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Oct 2016]

EDNRB Gene-Disease associations (from GenCC):

ABCD syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
Waardenburg syndrome type 4A
Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
Waardenburg syndrome type 2
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Waardenburg-Shah syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Hirschsprung disease, susceptibility to, 2
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

EDNRB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EDNRB	NM_000115.5 link	c.-51-6810G>A		intron_variant	Intron 1 of 7		NP_000106.1	P24530-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBI1-AS1	ENST00000607862.5 link	n.230+5516C>T		intron_variant	Intron 1 of 2	1
EDNRB	ENST00000646948.1 link	c.-51-6810G>A		intron_variant	Intron 1 of 7			ENSP00000493895.1		P24530-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15572

AN:

152052

Hom.:

880

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0759

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.0875

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.0606

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0944

Gnomad OTH

AF:

0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.102

AC:

15589

AN:

152170

Hom.:

884

Cov.:

AF XY:

0.102

AC XY:

7557

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.125

AC:

5185

AN:

41496

American (AMR)

AF:

0.0758

AC:

1160

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

679

AN:

3468

East Asian (EAS)

AF:

0.0879

AC:

455

AN:

5176

South Asian (SAS)

AF:

0.134

AC:

646

AN:

4824

European-Finnish (FIN)

AF:

0.0606

AC:

641

AN:

10578

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0944

AC:

6418

AN:

68010

Other (OTH)

AF:

0.119

AC:

252

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

726

1451

2177

2902

3628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0988

Hom.:

1350

Bravo

AF:

0.105

Asia WGS

AF:

0.105

AC:

365

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.1

(source)

DANN

Benign

0.90

PhyloP100

0.14

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over