rs1867655

Variant names:

• chr14-76471705-G-A
• rs1867655
• NM_001379180.1:c.577+9044G>A

Variant summary

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

The NM_001379180.1(ESRRB):​c.577+9044G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 152,308 control chromosomes in the GnomAD database, including 60,498 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 0.89 (60498 hom., cov: 34)
• Consequence: ESRRB NM_001379180.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 0 publications found

Genes affected

ESRRB (HGNC:3473): (estrogen related receptor beta) This gene encodes a protein with similarity to the estrogen receptor. Its function is unknown; however, a similar protein in mouse plays an essential role in placental development. [provided by RefSeq, Jul 2008]

ESRRB Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 35

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRB	NM_001379180.1	c.577+9044G>A		intron_variant	Intron 3 of 6	ENST00000644823.1	NP_001366109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRB	ENST00000644823.1	c.577+9044G>A		intron_variant	Intron 3 of 6		NM_001379180.1	ENSP00000493776.1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 135323 AN: 152190 Hom.: 60444 Cov.: 34

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.896

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.898

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.889 AC: 135435 AN: 152308 Hom.: 60498 Cov.: 34 AF XY: 0.893 AC XY: 66528 AN XY: 74464

African (AFR) AF: 0.954 AC: 39665 AN: 41578

American (AMR) AF: 0.906 AC: 13862 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3208 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5180

South Asian (SAS) AF: 0.965 AC: 4657 AN: 4824

European-Finnish (FIN) AF: 0.896 AC: 9514 AN: 10618

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56324 AN: 68016

Other (OTH) AF: 0.899 AC: 1902 AN: 2116

Alfa AF: 0.853 Hom.: 93598

Bravo AF: 0.893

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0030
DANN	Benign	0.38
PhyloP100		-2.6
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: rs1867655; hg19: chr14-76938048;