Genetic Variant ESRRB:c.50+27806A>G (chr14-76404257-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001379180.1(ESRRB):c.50+27806A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.891 in 151,940 control chromosomes in the GnomAD database, including 60,452 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 ( 60450 hom., cov: 31)

Exomes 𝑓: 1.0 ( 2 hom. )

Consequence

ESRRB
NM_001379180.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0110

Publications

10 publications found

Variant links:

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

ESRRB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379180.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ESRRB	NM_001379180.1	MANE Select	c.50+27806A>G	intron	N/A	NP_001366109.1
ESRRB	NM_004452.4		c.-131-139A>G	intron	N/A	NP_004443.3
ESRRB	NM_001411038.1		c.3-35084A>G	intron	N/A	NP_001397967.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ESRRB	ENST00000644823.1	MANE Select	c.50+27806A>G	intron	N/A	ENSP00000493776.1
ESRRB	ENST00000505752.6	TSL:1	n.-131-139A>G	intron	N/A	ENSP00000423004.1
ESRRB	ENST00000380887.7	TSL:5	c.-131-139A>G	intron	N/A	ENSP00000370270.2

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135235

AN:

151830

Hom.:

60415

Cov.:

show subpopulations

Gnomad AFR

AF:

0.809

Gnomad AMI

AF:

0.870

Gnomad AMR

AF:

0.936

Gnomad ASJ

AF:

0.960

Gnomad EAS

AF:

0.878

Gnomad SAS

AF:

0.893

Gnomad FIN

AF:

0.903

Gnomad MID

AF:

0.978

Gnomad NFE

AF:

0.925

Gnomad OTH

AF:

0.906

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.891

AC:

135317

AN:

151936

Hom.:

60450

Cov.:

AF XY:

0.890

AC XY:

66086

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.809

AC:

33513

AN:

41420

American (AMR)

AF:

0.936

AC:

14262

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.960

AC:

3329

AN:

3466

East Asian (EAS)

AF:

0.878

AC:

4553

AN:

5184

South Asian (SAS)

AF:

0.893

AC:

4296

AN:

4810

European-Finnish (FIN)

AF:

0.903

AC:

9476

AN:

10492

Middle Eastern (MID)

AF:

0.976

AC:

287

AN:

294

European-Non Finnish (NFE)

AF:

0.925

AC:

62901

AN:

68010

Other (OTH)

AF:

0.905

AC:

1907

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

737

1474

2212

2949

3686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.919

Hom.:

82079

Bravo

AF:

0.889

Asia WGS

AF:

0.888

AC:

3083

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.7

(source)

DANN

Benign

0.22

PhyloP100

-0.011

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over