NM_004451.5:c.743-36C>T

Variant names:

• chr11-64314965-C-T
• rs650008
• NM_004451.5:c.743-36C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.991 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.743-36C>T		intron	N/A	NP_004442.3
	ESRRA	NM_001282450.2		c.743-36C>T		intron	N/A	NP_001269379.1	P11474-1
	ESRRA	NM_001282451.2		c.740-36C>T		intron	N/A	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.743-36C>T		intron	N/A	ENSP00000000442.6	P11474-1
	ESRRA	ENST00000406310.6	TSL:1	c.992-36C>T		intron	N/A	ENSP00000385971.2	A0A6E1WCP9
	ESRRA	ENST00000405666.5	TSL:1	c.743-36C>T		intron	N/A	ENSP00000384851.1	P11474-1

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

GnomAD2 exomes AF: 0.940 AC: 210042 AN: 223508 AF XY: 0.939

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 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

African (AFR) AF: 0.572 AC: 18833 AN: 32926

American (AMR) AF: 0.974 AC: 41581 AN: 42708

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 25524 AN: 25670

East Asian (EAS) AF: 0.903 AC: 35024 AN: 38806

South Asian (SAS) AF: 0.817 AC: 69266 AN: 84750

European-Finnish (FIN) AF: 1.00 AC: 50107 AN: 50128

Middle Eastern (MID) AF: 0.972 AC: 4969 AN: 5114

European-Non Finnish (NFE) AF: 0.998 AC: 1100744 AN: 1102436

Other (OTH) AF: 0.954 AC: 56830 AN: 59562

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

African (AFR) AF: 0.589 AC: 24466 AN: 41530

American (AMR) AF: 0.946 AC: 14485 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 3450 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4736 AN: 5184

South Asian (SAS) AF: 0.805 AC: 3892 AN: 4832

European-Finnish (FIN) AF: 1.00 AC: 10627 AN: 10630

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.997 AC: 67843 AN: 68028

Other (OTH) AF: 0.906 AC: 1911 AN: 2110

Alfa AF: 0.932 Hom.: 20946

Bravo AF: 0.859

Asia WGS AF: 0.850 AC: 2958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.70
PhyloP100		0.035
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs650008; hg19: chr11-64082437;