rs731703

Variant names:

• chr11-64311234-G-A
• rs731703
• NM_004451.5:c.326-2717G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004451.5(ESRRA):​c.326-2717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,156 control chromosomes in the GnomAD database, including 4,678 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 0.22 (4678 hom., cov: 33)
• Consequence: ESRRA NM_004451.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRA	NM_004451.5	c.326-2717G>A		intron_variant	Intron 2 of 6	ENST00000000442.11	NP_004442.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRA	ENST00000000442.11	c.326-2717G>A		intron_variant	Intron 2 of 6	1	NM_004451.5	ENSP00000000442.6

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33397 AN: 152038 Hom.: 4680 Cov.: 33

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0874

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.219 AC: 33385 AN: 152156 Hom.: 4678 Cov.: 33 AF XY: 0.219 AC XY: 16281 AN XY: 74398

African (AFR) AF: 0.0579 AC: 2405 AN: 41536

American (AMR) AF: 0.181 AC: 2766 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 954 AN: 3470

East Asian (EAS) AF: 0.0875 AC: 453 AN: 5180

South Asian (SAS) AF: 0.300 AC: 1449 AN: 4826

European-Finnish (FIN) AF: 0.262 AC: 2776 AN: 10588

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21654 AN: 67964

Other (OTH) AF: 0.242 AC: 510 AN: 2104

Alfa AF: 0.263 Hom.: 971

Bravo AF: 0.205

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.6
DANN	Benign	0.84
PhyloP100		0.42
Mutation Taster		=100/0	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: rs731703; hg19: chr11-64078706;