13-77919725-AG-A

Variant names:

• chr13-77919725-AG-A
• rs367849777
• ENST00000377211.8:c.-111delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000377211.8(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 ENST00000377211.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.719
• Publications: 1 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]

OBI1-AS1 (HGNC:42700): (OBI1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR,Unknown,SD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377211.8. 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_000115.5		c.-51-1102delC		intron	N/A	NP_000106.1	P24530-1
	EDNRB	NM_001201397.2		c.-111delC		upstream_gene	N/A	NP_001188326.1	P24530-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EDNRB	ENST00000377211.8	TSL:1	c.-111delC		5_prime_UTR	Exon 1 of 8	ENSP00000366416.4	P24530-3
	OBI1-AS1	ENST00000607862.5	TSL:1	n.43delG		non_coding_transcript_exon	Exon 1 of 3
	EDNRB	ENST00000646948.1		c.-51-1102delC		intron	N/A	ENSP00000493895.1	P24530-1

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

African (AFR) AF: 0.0111 AC: 243 AN: 21810

American (AMR) AF: 0.00176 AC: 47 AN: 26672

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 23 AN: 17710

East Asian (EAS) AF: 0.00 AC: 0 AN: 32928

South Asian (SAS) AF: 0.000122 AC: 7 AN: 57552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37502

Middle Eastern (MID) AF: 0.00532 AC: 16 AN: 3008

European-Non Finnish (NFE) AF: 0.000219 AC: 148 AN: 676614

Other (OTH) AF: 0.00169 AC: 70 AN: 41436

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

African (AFR) AF: 0.0116 AC: 482 AN: 41526

American (AMR) AF: 0.00307 AC: 47 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68006

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000271 Hom.: 0

Bravo AF: 0.00432

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.72
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs367849777; hg19: chr13-78493860;