Genetic Variant ESRRB:c.50+28024T>C (chr14-76404475-T-C) – 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+28024T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,990 control chromosomes in the GnomAD database, including 15,447 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 0.44 ( 15428 hom., cov: 31)

Exomes 𝑓: 0.53 ( 19 hom. )

Consequence

ESRRB
NM_001379180.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.136

Publications

12 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 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	UniProt
ESRRB	NM_001379180.1	MANE Select	c.50+28024T>C	intron	N/A	NP_001366109.1	A0A2R8Y491
ESRRB	NM_004452.4		c.-68+16T>C	intron	N/A	NP_004443.3
ESRRB	NM_001411038.1		c.3-34866T>C	intron	N/A	NP_001397967.1	E7EWD9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ESRRB	ENST00000644823.1	MANE Select	c.50+28024T>C	intron	N/A	ENSP00000493776.1	A0A2R8Y491
ESRRB	ENST00000505752.6	TSL:1	n.-68+16T>C	intron	N/A	ENSP00000423004.1	O95718-2
ESRRB	ENST00000380887.7	TSL:5	c.-68+16T>C	intron	N/A	ENSP00000370270.2	O95718-1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67062

AN:

151744

Hom.:

15417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.400

Gnomad AMI

AF:

0.489

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.589

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.431

Gnomad OTH

AF:

0.419

GnomAD4 exome

AF:

0.531

AC:

AN:

128

Hom.:

Cov.:

AF XY:

0.407

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)

AF:

0.532

AC:

AN:

124

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.568

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.442

AC:

67110

AN:

151862

Hom.:

15428

Cov.:

AF XY:

0.449

AC XY:

33310

AN XY:

74192

show subpopulations

African (AFR)

AF:

0.400

AC:

16558

AN:

41382

American (AMR)

AF:

0.397

AC:

6064

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

1185

AN:

3464

East Asian (EAS)

AF:

0.816

AC:

4215

AN:

5168

South Asian (SAS)

AF:

0.588

AC:

2829

AN:

4814

European-Finnish (FIN)

AF:

0.523

AC:

5492

AN:

10504

Middle Eastern (MID)

AF:

0.373

AC:

109

AN:

292

European-Non Finnish (NFE)

AF:

0.431

AC:

29318

AN:

67962

Other (OTH)

AF:

0.425

AC:

895

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1840

3680

5520

7360

9200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.436

Hom.:

23147

Bravo

AF:

0.430

Asia WGS

AF:

0.680

AC:

2365

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.3

(source)

DANN

Benign

0.69

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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