rs61760172

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001379180.1(ESRRB):c.206C>T(p.Ala69Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000301 in 1,612,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

ESRRB
NM_001379180.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:6

Conservation

PhyloP100: 7.85

Publications

5 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066467524).

BP6

Variant 14-76439496-C-T is Benign according to our data. Variant chr14-76439496-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 178342.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0015 (229/152358) while in subpopulation AFR AF = 0.00519 (216/41586). AF 95% confidence interval is 0.00463. There are 0 homozygotes in GnomAd4. There are 102 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRRB	NM_001379180.1	MANE Select	c.206C>T	p.Ala69Val	missense	Exon 2 of 7	NP_001366109.1	A0A2R8Y491
ESRRB	NM_004452.4		c.143C>T	p.Ala48Val	missense	Exon 4 of 11	NP_004443.3
ESRRB	NM_001411038.1		c.158C>T	p.Ala53Val	missense	Exon 2 of 7	NP_001397967.1	E7EWD9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRRB	ENST00000644823.1	MANE Select	c.206C>T	p.Ala69Val	missense	Exon 2 of 7	ENSP00000493776.1	A0A2R8Y491
ESRRB	ENST00000509242.5	TSL:1	c.143C>T	p.Ala48Val	missense	Exon 2 of 9	ENSP00000422488.1	O95718-1
ESRRB	ENST00000505752.6	TSL:1	n.143C>T		non_coding_transcript_exon	Exon 4 of 12	ENSP00000423004.1	O95718-2

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

229

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00521

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000347

AC:

AN:

244822

AF XY:

0.000300

show subpopulations

Gnomad AFR exome

AF:

0.00496

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000363

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000176

AC:

257

AN:

1460276

Hom.:

Cov.:

AF XY:

0.000167

AC XY:

121

AN XY:

726544

show subpopulations

African (AFR)

AF:

0.00618

AC:

207

AN:

33474

American (AMR)

AF:

0.000201

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000696

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000162

AC:

AN:

1111858

Other (OTH)

AF:

0.000282

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00150

AC:

229

AN:

152358

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00519

AC:

216

AN:

41586

American (AMR)

AF:

0.000588

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68040

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000332

Hom.:

Bravo

AF:

0.00167

ESP6500AA

AF:

0.00364

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000446

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Autosomal recessive nonsyndromic hearing loss 35 (1)

ESRRB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Benign

0.076

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0066

MetaSVM

Uncertain

-0.073

MutationAssessor

Benign

1.7

PhyloP100

7.9

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.85

REVEL

Benign

0.27

Sift

Benign

0.054

Sift4G

Benign

0.31

Polyphen

0.0040

Vest4

0.52

MVP

0.73

MPC

0.39

ClinPred

0.024

GERP RS

5.2

PromoterAI

-0.017

Neutral

(source)

gMVP

0.42

Mutation Taster

=56/44

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over