13-77919725-AG-A

Position:

• chr13-77919725-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001201397.1(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 NM_001201397.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.719

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]

OBI1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EDNRB	NM_001201397.1	c.-111delC		5_prime_UTR_variant	1/8		NP_001188326.1
EDNRB	NM_000115.5	c.-51-1102delC		intron_variant			NP_000106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EDNRB	ENST00000377211.8	c.-111delC		5_prime_UTR_variant	1/8	1		ENSP00000366416.4
OBI1-AS1	ENST00000607862.5	n.43delG		non_coding_transcript_exon_variant	1/3	1
EDNRB	ENST00000646948.1	c.-51-1102delC		intron_variant				ENSP00000493895.1

Frequencies

GnomAD3 genomes AF: 0.00364 AC: 553 AN: 152084 Hom.: 2 Cov.: 32

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.: 6 Cov.: 12 AF XY: 0.000602 AC XY: 274 AN XY: 455504

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.00176

Gnomad4 ASJ exome AF: 0.00130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000122

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.00169

GnomAD4 genome AF: 0.00364 AC: 554 AN: 152202 Hom.: 2 Cov.: 32 AF XY: 0.00364 AC XY: 271 AN XY: 74416

Gnomad4 AFR AF: 0.0116

Gnomad4 AMR AF: 0.00307

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.000271 Hom.: 0

Bravo AF: 0.00432

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs367849777; hg19: chr13-78493860;