11-64314965-C-T

Position:

• chr11-64314965-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.743-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 1,594,400 control chromosomes in the GnomAD database, including 747,017 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 0.87 (60175 hom., cov: 34)
  • Exomes 𝑓: 0.97 (686842 hom.)
• Consequence: ESRRA NM_004451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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]

ESRRA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRA	NM_004451.5	c.743-36C>T		intron_variant		ENST00000000442.11	NP_004442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRA	ENST00000000442.11	c.743-36C>T		intron_variant		1	NM_004451.5	ENSP00000000442.6

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132539 AN: 152182 Hom.: 60155 Cov.: 34

Gnomad AFR AF: 0.589

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.946

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.804

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.905

GnomAD3 exomes AF: 0.940 AC: 210042 AN: 223508 Hom.: 100054 AF XY: 0.939 AC XY: 114654 AN XY: 122040

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.976

Gnomad ASJ exome AF: 0.994

Gnomad EAS exome AF: 0.924

Gnomad SAS exome AF: 0.814

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.997

Gnomad OTH exome AF: 0.965

GnomAD4 exome AF: 0.973 AC: 1402878 AN: 1442100 Hom.: 686842 Cov.: 62 AF XY: 0.969 AC XY: 693928 AN XY: 715836

Gnomad4 AFR exome AF: 0.572

Gnomad4 AMR exome AF: 0.974

Gnomad4 ASJ exome AF: 0.994

Gnomad4 EAS exome AF: 0.903

Gnomad4 SAS exome AF: 0.817

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.954

GnomAD4 genome AF: 0.871 AC: 132607 AN: 152300 Hom.: 60175 Cov.: 34 AF XY: 0.873 AC XY: 65001 AN XY: 74490

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.946

Gnomad4 ASJ AF: 0.994

Gnomad4 EAS AF: 0.914

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.906

Alfa AF: 0.942 Hom.: 19330

Bravo AF: 0.859

Asia WGS AF: 0.850 AC: 2958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs650008; hg19: chr11-64082437;