rs2276014

Variant names:

• chr11-64313973-G-A
• rs2276014
• NM_004451.5:c.348G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_004451.5(ESRRA):​c.348G>A​(p.Pro116Pro) 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
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004451.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRA	NM_004451.5	MANE Select	c.348G>A	p.Pro116Pro	synonymous	Exon 3 of 7	NP_004442.3
	ESRRA	NM_001282450.2		c.348G>A	p.Pro116Pro	synonymous	Exon 3 of 7	NP_001269379.1	P11474-1
	ESRRA	NM_001282451.2		c.348G>A	p.Pro116Pro	synonymous	Exon 3 of 7	NP_001269380.1	P11474-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRA	ENST00000000442.11	TSL:1 MANE Select	c.348G>A	p.Pro116Pro	synonymous	Exon 3 of 7	ENSP00000000442.6	P11474-1
	ESRRA	ENST00000406310.6	TSL:1	c.600G>A	p.Pro200Pro	synonymous	Exon 3 of 7	ENSP00000385971.2	A0A6E1WCP9
	ESRRA	ENST00000405666.5	TSL:1	c.348G>A	p.Pro116Pro	synonymous	Exon 3 of 7	ENSP00000384851.1	P11474-1

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

GnomAD2 exomes AF: 0.131 AC: 25654 AN: 195124 AF XY: 0.134

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 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

African (AFR) AF: 0.0373 AC: 1223 AN: 32774

American (AMR) AF: 0.108 AC: 4304 AN: 39824

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 3234 AN: 25486

East Asian (EAS) AF: 0.104 AC: 3959 AN: 38052

South Asian (SAS) AF: 0.0845 AC: 6950 AN: 82202

European-Finnish (FIN) AF: 0.159 AC: 8018 AN: 50482

Middle Eastern (MID) AF: 0.178 AC: 840 AN: 4732

European-Non Finnish (NFE) AF: 0.162 AC: 177332 AN: 1094048

Other (OTH) AF: 0.153 AC: 9007 AN: 58914

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

African (AFR) AF: 0.0430 AC: 1786 AN: 41556

American (AMR) AF: 0.129 AC: 1976 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3472

East Asian (EAS) AF: 0.110 AC: 567 AN: 5170

South Asian (SAS) AF: 0.0717 AC: 346 AN: 4824

European-Finnish (FIN) AF: 0.164 AC: 1735 AN: 10596

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10919 AN: 67986

Other (OTH) AF: 0.155 AC: 328 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	10
DANN	Benign	0.93
PhyloP100		-0.17
PromoterAI		0.033	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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