rs2276014

Positions:

• chr11-64313973-G-A
• chr11-64313973-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004451.5(ESRRA):​c.348G>A​(p.Pro116=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 1,578,746 control chromosomes in the GnomAD database, including 18,325 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 0.12 (1387 hom., cov: 33)
  • Exomes 𝑓: 0.15 (16938 hom.)
• Consequence: ESRRA NM_004451.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

Genes affected

ESRRA (HGNC:3471): (estrogen related receptor alpha) The protein encoded by this gene is a nuclear receptor that is most closely related to the estrogen receptor. This protein acts as a site-specific transcription factor and interacts with members of the PGC-1 family of transcription cofactors to regulate the expression of most genes involved in cellular energy production as well as in the process of mitochondrial biogenesis. A processed pseudogene of ESRRA is located on chromosome 13q12.1. [provided by RefSeq, Jun 2019]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.171 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESRRA	NM_004451.5	c.348G>A	p.Pro116=	synonymous_variant	3/7	ENST00000000442.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRRA	ENST00000000442.11	c.348G>A	p.Pro116=	synonymous_variant	3/7	1	NM_004451.5	P4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18204 AN: 152114 Hom.: 1388 Cov.: 33

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.131 AC: 25654 AN: 195124 Hom.: 1865 AF XY: 0.134 AC XY: 14180 AN XY: 105618

Gnomad AFR exome AF: 0.0399

Gnomad AMR exome AF: 0.108

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.0874

Gnomad FIN exome AF: 0.158

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.151 AC: 214867 AN: 1426514 Hom.: 16938 Cov.: 32 AF XY: 0.150 AC XY: 105921 AN XY: 706530

Gnomad4 AFR exome AF: 0.0373

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0845

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.120 AC: 18207 AN: 152232 Hom.: 1387 Cov.: 33 AF XY: 0.119 AC XY: 8876 AN XY: 74424

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0717

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.155

Alfa AF: 0.124 Hom.: 616

Bravo AF: 0.115

Asia WGS AF: 0.115 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.93
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

Publications

LitVar

Other links and lift over

dbSNP: rs2276014; hg19: chr11-64081445; COSMIC: COSV50005850; COSMIC: COSV50005850;