rs3027111

Variant names:

• chr13-77907733-C-T
• rs3027111
• NM_001122659.3:c.484-4126G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001201397.2(EDNRB):​c.754-4126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,504 control chromosomes in the GnomAD database, including 4,025 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 0.22 (4025 hom., cov: 31)
• Consequence: EDNRB NM_001201397.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0950
• Publications: 8 publications found

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-AS1 (HGNC:49045): (EDNRB antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001201397.2. 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_001122659.3	MANE Select	c.484-4126G>A		intron	N/A	NP_001116131.1
	EDNRB	NM_001201397.2		c.754-4126G>A		intron	N/A	NP_001188326.1
	EDNRB	NM_000115.5		c.484-4126G>A		intron	N/A	NP_000106.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	ENST00000646607.2	MANE Select	c.484-4126G>A		intron	N/A	ENSP00000493527.1
	EDNRB	ENST00000377211.8	TSL:1	c.754-4126G>A		intron	N/A	ENSP00000366416.4
	EDNRB	ENST00000626030.1	TSL:1	c.484-4126G>A		intron	N/A	ENSP00000486202.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32643 AN: 151386 Hom.: 4021 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.216 AC: 32669 AN: 151504 Hom.: 4025 Cov.: 31 AF XY: 0.222 AC XY: 16429 AN XY: 74010

African (AFR) AF: 0.244 AC: 10087 AN: 41318

American (AMR) AF: 0.262 AC: 3987 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3466

East Asian (EAS) AF: 0.565 AC: 2884 AN: 5100

South Asian (SAS) AF: 0.265 AC: 1273 AN: 4800

European-Finnish (FIN) AF: 0.225 AC: 2356 AN: 10492

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11093 AN: 67824

Other (OTH) AF: 0.198 AC: 416 AN: 2106

Alfa AF: 0.181 Hom.: 3205

Bravo AF: 0.221

Asia WGS AF: 0.337 AC: 1169 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.33
PhyloP100		0.095
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3027111; hg19: chr13-78481868;