13-77896215-A-G

Variant names:

• chr13-77896215-A-G
• rs4885491
• NM_001122659.3:c.*1985T>C

Variant summary

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

The NM_001122659.3(EDNRB):​c.*1985T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 242,920 control chromosomes in the GnomAD database, including 97,219 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 0.90 (60989 hom., cov: 31)
  • Exomes 𝑓: 0.89 (36230 hom.)
• Consequence: EDNRB NM_001122659.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	NM_001122659.3	MANE Select	c.*1985T>C		3_prime_UTR	Exon 7 of 7	NP_001116131.1
	EDNRB	NM_001201397.2		c.*1985T>C		3_prime_UTR	Exon 8 of 8	NP_001188326.1
	EDNRB	NM_000115.5		c.*1985T>C		3_prime_UTR	Exon 8 of 8	NP_000106.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	ENST00000646607.2	MANE Select	c.*1985T>C		3_prime_UTR	Exon 7 of 7	ENSP00000493527.1
	EDNRB	ENST00000377211.8	TSL:1	c.*1985T>C		3_prime_UTR	Exon 8 of 8	ENSP00000366416.4
	EDNRB	ENST00000646605.1		c.*1985T>C		3_prime_UTR	Exon 8 of 8	ENSP00000494278.1

Frequencies

GnomAD3 genomes AF: 0.896 AC: 135924 AN: 151734 Hom.: 60944 Cov.: 31

Gnomad AFR AF: 0.910

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.892

GnomAD4 exome AF: 0.892 AC: 81215 AN: 91070 Hom.: 36230 Cov.: 3 AF XY: 0.891 AC XY: 43510 AN XY: 48840

African (AFR) AF: 0.914 AC: 2360 AN: 2582

American (AMR) AF: 0.913 AC: 2048 AN: 2242

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2177 AN: 2568

East Asian (EAS) AF: 0.985 AC: 5249 AN: 5330

South Asian (SAS) AF: 0.935 AC: 1547 AN: 1654

European-Finnish (FIN) AF: 0.887 AC: 2176 AN: 2452

Middle Eastern (MID) AF: 0.899 AC: 372 AN: 414

European-Non Finnish (NFE) AF: 0.884 AC: 60586 AN: 68540

Other (OTH) AF: 0.889 AC: 4700 AN: 5288

GnomAD4 genome AF: 0.896 AC: 136025 AN: 151850 Hom.: 60989 Cov.: 31 AF XY: 0.897 AC XY: 66576 AN XY: 74218

African (AFR) AF: 0.910 AC: 37738 AN: 41476

American (AMR) AF: 0.905 AC: 13780 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2925 AN: 3470

East Asian (EAS) AF: 0.977 AC: 5030 AN: 5150

South Asian (SAS) AF: 0.931 AC: 4468 AN: 4798

European-Finnish (FIN) AF: 0.884 AC: 9302 AN: 10526

Middle Eastern (MID) AF: 0.915 AC: 269 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 59886 AN: 67880

Other (OTH) AF: 0.888 AC: 1873 AN: 2110

Alfa AF: 0.881 Hom.: 64131

Bravo AF: 0.898

Asia WGS AF: 0.928 AC: 3190 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.50
PhyloP100		0.20
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: rs4885491; hg19: chr13-78470350;