rs11600990

Positions:

• chr11-64315335-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004451.5(ESRRA):​c.1012+65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,476,794 control chromosomes in the GnomAD database, including 17,438 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 (1390 hom., cov: 34)
  • Exomes 𝑓: 0.15 (16048 hom.)
• Consequence: ESRRA NM_004451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.252

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• 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.1012+65C>T		intron_variant		ENST00000000442.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRRA	ENST00000000442.11	c.1012+65C>T		intron_variant		1	NM_004451.5	P4

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18217 AN: 152154 Hom.: 1391 Cov.: 34

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.153 AC: 202279 AN: 1324522 Hom.: 16048 AF XY: 0.152 AC XY: 98547 AN XY: 647694

Gnomad4 AFR exome AF: 0.0363

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.0850

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.120 AC: 18220 AN: 152272 Hom.: 1390 Cov.: 34 AF XY: 0.119 AC XY: 8884 AN XY: 74450

Gnomad4 AFR AF: 0.0429

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.156

Alfa AF: 0.154 Hom.: 3934

Bravo AF: 0.115

Asia WGS AF: 0.116 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.1
DANN	Benign	0.73

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: rs11600990; hg19: chr11-64082807; COSMIC: COSV50005877; COSMIC: COSV50005877;