NM_001122659.3:c.*1985T>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001122659.3(EDNRB):​c.*1985T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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>A		3_prime_UTR	Exon 7 of 7	NP_001116131.1
	EDNRB	NM_001201397.2		c.*1985T>A		3_prime_UTR	Exon 8 of 8	NP_001188326.1
	EDNRB	NM_000115.5		c.*1985T>A		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>A		3_prime_UTR	Exon 7 of 7	ENSP00000493527.1
	EDNRB	ENST00000377211.8	TSL:1	c.*1985T>A		3_prime_UTR	Exon 8 of 8	ENSP00000366416.4
	EDNRB	ENST00000646605.1		c.*1985T>A		3_prime_UTR	Exon 8 of 8	ENSP00000494278.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 91236 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 48906

African (AFR) AF: 0.00 AC: 0 AN: 2582

American (AMR) AF: 0.00 AC: 0 AN: 2250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2572

East Asian (EAS) AF: 0.00 AC: 0 AN: 5330

South Asian (SAS) AF: 0.00 AC: 0 AN: 1654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 416

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68678

Other (OTH) AF: 0.00 AC: 0 AN: 5298

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		0.20

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;