rs3027094

Variant names:

• chr13-77896654-T-C
• rs3027094
• NM_001122659.3:c.*1546A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001122659.3(EDNRB):​c.*1546A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,489,870 control chromosomes in the GnomAD database, including 150 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (87 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (63 hom.)
• Consequence: EDNRB NM_001122659.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.516
• Publications: 2 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 13-77896654-T-C is Benign according to our data. Variant chr13-77896654-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 312454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122659.3. 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.*1546A>G		3_prime_UTR	Exon 7 of 7	NP_001116131.1	P24530-1
	EDNRB	NM_001201397.2		c.*1546A>G		3_prime_UTR	Exon 8 of 8	NP_001188326.1	P24530-3
	EDNRB	NM_000115.5		c.*1546A>G		3_prime_UTR	Exon 8 of 8	NP_000106.1	P24530-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	ENST00000646607.2	MANE Select	c.*1546A>G		3_prime_UTR	Exon 7 of 7	ENSP00000493527.1	P24530-1
	EDNRB	ENST00000377211.8	TSL:1	c.*1546A>G		3_prime_UTR	Exon 8 of 8	ENSP00000366416.4	P24530-3
	EDNRB	ENST00000626030.1	TSL:1	c.1195-96A>G		intron	N/A	ENSP00000486202.1	P24530-2

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2630 AN: 152008 Hom.: 86 Cov.: 33

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00276 AC: 3691 AN: 1337744 Hom.: 63 Cov.: 31 AF XY: 0.00254 AC XY: 1669 AN XY: 658230

African (AFR) AF: 0.0621 AC: 1798 AN: 28954

American (AMR) AF: 0.00862 AC: 244 AN: 28312

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 128 AN: 23396

East Asian (EAS) AF: 0.00 AC: 0 AN: 33132

South Asian (SAS) AF: 0.000568 AC: 40 AN: 70402

European-Finnish (FIN) AF: 0.0000796 AC: 3 AN: 37700

Middle Eastern (MID) AF: 0.0105 AC: 45 AN: 4284

European-Non Finnish (NFE) AF: 0.000984 AC: 1039 AN: 1056044

Other (OTH) AF: 0.00710 AC: 394 AN: 55520

GnomAD4 genome AF: 0.0173 AC: 2638 AN: 152126 Hom.: 87 Cov.: 33 AF XY: 0.0164 AC XY: 1216 AN XY: 74356

African (AFR) AF: 0.0562 AC: 2333 AN: 41524

American (AMR) AF: 0.0102 AC: 155 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00119 AC: 81 AN: 67960

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00980 Hom.: 13

Bravo AF: 0.0201

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hirschsprung disease, susceptibility to, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		0.52
Mutation Taster		=99/1	polymorphism

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: rs3027094; hg19: chr13-78470789;