Genetic Variant ENST00000377211.8:c.-111delC (chr13-77919725-AG-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000377211.8(EDNRB):c.-111delC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,067,434 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 6 hom. )

Consequence

EDNRB
ENST00000377211.8 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.719

Publications

1 publications found

Variant links:

Genes affected

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 links:

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

OBI1-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000377211.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 13-77919725-AG-A is Benign according to our data. Variant chr13-77919725-AG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1223528.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00364 (554/152202) while in subpopulation AFR AF = 0.0116 (482/41526). AF 95% confidence interval is 0.0108. There are 2 homozygotes in GnomAd4. There are 271 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 Unknown,SD,AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377211.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	NM_000115.5		c.-51-1102delC		intron	N/A	NP_000106.1	P24530-1
	EDNRB	NM_001201397.2		c.-111delC		upstream_gene	N/A	NP_001188326.1	P24530-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EDNRB	ENST00000377211.8	TSL:1	c.-111delC	5_prime_UTR	Exon 1 of 8	ENSP00000366416.4	P24530-3
OBI1-AS1	ENST00000607862.5	TSL:1	n.43delG	non_coding_transcript_exon	Exon 1 of 3
EDNRB	ENST00000646948.1		c.-51-1102delC	intron	N/A	ENSP00000493895.1	P24530-1

Frequencies

GnomAD3 genomes

AF:

0.00364

AC:

553

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00307

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000959

GnomAD4 exome

AF:

0.000605

AC:

554

AN:

915232

Hom.:

Cov.:

AF XY:

0.000602

AC XY:

274

AN XY:

455504

show subpopulations

African (AFR)

AF:

0.0111

AC:

243

AN:

21810

American (AMR)

AF:

0.00176

AC:

AN:

26672

Ashkenazi Jewish (ASJ)

AF:

0.00130

AC:

AN:

17710

East Asian (EAS)

AF:

0.00

AC:

AN:

32928

South Asian (SAS)

AF:

0.000122

AC:

AN:

57552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37502

Middle Eastern (MID)

AF:

0.00532

AC:

AN:

3008

European-Non Finnish (NFE)

AF:

0.000219

AC:

148

AN:

676614

Other (OTH)

AF:

0.00169

AC:

AN:

41436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

100

125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00364

AC:

554

AN:

152202

Hom.:

Cov.:

AF XY:

0.00364

AC XY:

271

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0116

AC:

482

AN:

41526

American (AMR)

AF:

0.00307

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000208

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68006

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000271

Hom.:

Bravo

AF:

0.00432

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.72

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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