Genetic Variant ESRRB:p.Gly308Gly (chr14-76491520-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_001379180.1(ESRRB):c.924C>T(p.Gly308Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G308G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ESRRB
NM_001379180.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.69

Publications

0 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: Ambry Genetics, G2P, 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

new If you want to explore the variant's impact on the transcript NM_001379180.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP7

Synonymous conserved (PhyloP=2.69 with no splicing effect.

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.924C>T	p.Gly308Gly	synonymous	Exon 6 of 7	NP_001366109.1	A0A2R8Y491
ESRRB	NM_004452.4		c.861C>T	p.Gly287Gly	synonymous	Exon 8 of 11	NP_004443.3
ESRRB	NM_001411038.1		c.876C>T	p.Gly292Gly	synonymous	Exon 6 of 7	NP_001397967.1	E7EWD9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ESRRB	ENST00000644823.1	MANE Select	c.924C>T	p.Gly308Gly	synonymous	Exon 6 of 7	ENSP00000493776.1	A0A2R8Y491
ESRRB	ENST00000509242.5	TSL:1	c.861C>T	p.Gly287Gly	synonymous	Exon 6 of 9	ENSP00000422488.1	O95718-1
ESRRB	ENST00000505752.6	TSL:1	n.861C>T		non_coding_transcript_exon	Exon 8 of 12	ENSP00000423004.1	O95718-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448296

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718980

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33356

American (AMR)

AF:

0.00

AC:

AN:

42534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25804

East Asian (EAS)

AF:

0.00

AC:

AN:

39254

South Asian (SAS)

AF:

0.00

AC:

AN:

83850

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52434

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5210

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1105972

Other (OTH)

AF:

0.0000167

AC:

AN:

59882

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

8.1

(source)

DANN

Benign

0.80

PhyloP100

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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