ENST00000366940.6:c.-230+38380A>G

Variant names:

• chr1-217099287-T-C
• rs12033461
• ENST00000366940.6:c.-230+38380A>G

Variant summary

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

The ENST00000366940.6(ESRRG):​c.-230+38380A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 151,490 control chromosomes in the GnomAD database, including 1,259 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 0.11 (1259 hom., cov: 32)
• Consequence: ESRRG ENST00000366940.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.800
• Publications: 5 publications found

Genes affected

ESRRG (HGNC:3474): (estrogen related receptor gamma) This gene encodes a member of the estrogen receptor-related receptor (ESRR) family, which belongs to the nuclear hormone receptor superfamily. All members of the ESRR family share an almost identical DNA binding domain, which is composed of two C4-type zinc finger motifs. The ESRR members are orphan nuclear receptors; they bind to the estrogen response element and steroidogenic factor 1 response element, and activate genes controlled by both response elements in the absence of any ligands. The ESRR family is closely related to the estrogen receptor (ER) family. They share target genes, co-regulators and promoters, and by targeting the same set of genes, the ESRRs seem to interfere with the ER-mediated estrogen response in various ways. It has been reported that the family member encoded by this gene functions as a transcriptional activator of DNA cytosine-5-methyltransferases 1 (Dnmt1) expression by direct binding to its response elements in the DNMT1 promoters, modulates cell proliferation and estrogen signaling in breast cancer, and negatively regulates bone morphogenetic protein 2-induced osteoblast differentiation and bone formation. Multiple alternatively spliced transcript variants have been identified, which mainly differ at the 5' end and some of which encode protein isoforms differing in the N-terminal region. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRG	NM_001134285.3	c.-230+38380A>G		intron_variant	Intron 1 of 8		NP_001127757.1
ESRRG	NM_001243510.3	c.-224+38380A>G		intron_variant	Intron 1 of 8		NP_001230439.1
ESRRG	NM_001243511.3	c.-106+38380A>G		intron_variant	Intron 1 of 7		NP_001230440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRG	ENST00000366940.6	c.-230+38380A>G		intron_variant	Intron 1 of 8	1		ENSP00000355907.2
ESRRG	ENST00000493603.5	c.-224+38380A>G		intron_variant	Intron 1 of 8	1		ENSP00000419594.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17177 AN: 151372 Hom.: 1257 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0736

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.0924

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.0962

Gnomad NFE AF: 0.0753

Gnomad OTH AF: 0.0998

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

GnomAD4 genome AF: 0.114 AC: 17216 AN: 151490 Hom.: 1259 Cov.: 32 AF XY: 0.114 AC XY: 8466 AN XY: 73948

African (AFR) AF: 0.192 AC: 7901 AN: 41242

American (AMR) AF: 0.0815 AC: 1237 AN: 15172

Ashkenazi Jewish (ASJ) AF: 0.0736 AC: 255 AN: 3464

East Asian (EAS) AF: 0.235 AC: 1209 AN: 5140

South Asian (SAS) AF: 0.0912 AC: 439 AN: 4812

European-Finnish (FIN) AF: 0.0733 AC: 763 AN: 10414

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0753 AC: 5116 AN: 67938

Other (OTH) AF: 0.105 AC: 222 AN: 2106

Alfa AF: 0.0851 Hom.: 1080

Bravo AF: 0.121

Asia WGS AF: 0.177 AC: 614 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.61
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12033461; hg19: chr1-217272629;