14-76371349-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004452.4(ESRRB):​c.-369G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000886 in 152,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)
Exomes 𝑓: 0.010 ( 0 hom. )

Consequence

ESRRB
NM_004452.4 5_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.927
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ESRRBNM_004452.4 linkuse as main transcriptc.-369G>A 5_prime_UTR_variant 1/11 NP_004443.3
ESRRBNM_001411038.1 linkuse as main transcriptc.2+60433G>A intron_variant NP_001397967.1
ESRRBXM_047431079.1 linkuse as main transcriptc.-67-36194G>A intron_variant XP_047287035.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ESRRBENST00000380887.7 linkuse as main transcriptc.-369G>A 5_prime_UTR_variant 1/115 ENSP00000370270 O95718-1
ESRRBENST00000512784.6 linkuse as main transcriptc.2+60433G>A intron_variant 5 ENSP00000424992
ESRRBENST00000505752.6 linkuse as main transcript upstream_gene_variant 1 ENSP00000423004 O95718-2

Frequencies

GnomAD3 genomes
AF:
0.000887
AC:
135
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00113
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00548
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000647
Gnomad OTH
AF:
0.00143
GnomAD4 exome
AF:
0.0100
AC:
1
AN:
100
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
74
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0128
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000880
AC:
134
AN:
152312
Hom.:
0
Cov.:
32
AF XY:
0.000993
AC XY:
74
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00113
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00548
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00331
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000647
Gnomad4 OTH
AF:
0.00142
Bravo
AF:
0.000914

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 35 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.15
DANN
Benign
0.67

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs111446027; hg19: chr14-76837692; API