rs61742642

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379180.1(ESRRB):c.1219C>T(p.Pro407Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,613,184 control chromosomes in the GnomAD database, including 4,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 357 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4033 hom. )

Consequence

ESRRB
NM_001379180.1 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 7.91

Publications

20 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:

ENSG00000259124 (HGNC:):

ENSG00000259124 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005125433).

BP6

Variant 14-76498312-C-T is Benign according to our data. Variant chr14-76498312-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.124 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	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRRB	NM_001379180.1	MANE Select	c.1219C>T	p.Pro407Ser	missense	Exon 7 of 7	NP_001366109.1	A0A2R8Y491
ESRRB	NM_004452.4		c.1156C>T	p.Pro386Ser	missense	Exon 9 of 11	NP_004443.3
ESRRB	NM_001411038.1		c.1171C>T	p.Pro391Ser	missense	Exon 7 of 7	NP_001397967.1	E7EWD9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRRB	ENST00000644823.1	MANE Select	c.1219C>T	p.Pro407Ser	missense	Exon 7 of 7	ENSP00000493776.1	A0A2R8Y491
ESRRB	ENST00000509242.5	TSL:1	c.1156C>T	p.Pro386Ser	missense	Exon 7 of 9	ENSP00000422488.1	O95718-1
ESRRB	ENST00000505752.6	TSL:1	n.1156C>T		non_coding_transcript_exon	Exon 9 of 12	ENSP00000423004.1	O95718-2

Frequencies

GnomAD3 genomes

AF:

0.0616

AC:

9371

AN:

152182

Hom.:

357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.0704

Gnomad FIN

AF:

0.0488

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0680

Gnomad OTH

AF:

0.0659

GnomAD2 exomes

AF:

0.0766

AC:

18998

AN:

248148

AF XY:

0.0742

show subpopulations

Gnomad AFR exome

AF:

0.0228

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.0532

Gnomad EAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0507

Gnomad NFE exome

AF:

0.0692

Gnomad OTH exome

AF:

0.0753

GnomAD4 exome

AF:

0.0712

AC:

104043

AN:

1460884

Hom.:

4033

Cov.:

AF XY:

0.0709

AC XY:

51493

AN XY:

726768

show subpopulations

African (AFR)

AF:

0.0215

AC:

718

AN:

33472

American (AMR)

AF:

0.136

AC:

6086

AN:

44594

Ashkenazi Jewish (ASJ)

AF:

0.0565

AC:

1477

AN:

26122

East Asian (EAS)

AF:

0.0961

AC:

3813

AN:

39668

South Asian (SAS)

AF:

0.0679

AC:

5853

AN:

86246

European-Finnish (FIN)

AF:

0.0527

AC:

2788

AN:

52874

Middle Eastern (MID)

AF:

0.0539

AC:

311

AN:

5766

European-Non Finnish (NFE)

AF:

0.0708

AC:

78734

AN:

1111786

Other (OTH)

AF:

0.0706

AC:

4263

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

6137

12273

18410

24546

30683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3004

6008

9012

12016

15020

<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:

0.0615

AC:

9372

AN:

152300

Hom.:

357

Cov.:

AF XY:

0.0645

AC XY:

4806

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0243

AC:

1012

AN:

41584

American (AMR)

AF:

0.129

AC:

1969

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0504

AC:

175

AN:

3472

East Asian (EAS)

AF:

0.101

AC:

521

AN:

5164

South Asian (SAS)

AF:

0.0705

AC:

340

AN:

4826

European-Finnish (FIN)

AF:

0.0488

AC:

518

AN:

10614

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0680

AC:

4623

AN:

68014

Other (OTH)

AF:

0.0652

AC:

138

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

461

921

1382

1842

2303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0637

Hom.:

741

Bravo

AF:

0.0637

TwinsUK

AF:

0.0763

AC:

283

ALSPAC

AF:

0.0747

AC:

288

ESP6500AA

AF:

0.0252

AC:

111

ESP6500EA

AF:

0.0680

AC:

585

ExAC

AF:

0.0712

AC:

8643

Asia WGS

AF:

0.108

AC:

375

AN:

3478

EpiCase

AF:

0.0677

EpiControl

AF:

0.0715

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Autosomal recessive nonsyndromic hearing loss 35 (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.64

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0051

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

PhyloP100

7.9

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.4

REVEL

Pathogenic

0.68

Sift

Benign

0.45

Sift4G

Benign

0.72

Polyphen

0.60

Vest4

0.34

MPC

0.60

ClinPred

0.026

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.55

Mutation Taster

=93/7

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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