rs1561189

Variant names:

• chr1-216959173-A-C
• rs1561189
• ENST00000359162.6:c.-105-19500T>G

Variant summary

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

The NM_206594.3(ESRRG):​c.-223-19500T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,684 control chromosomes in the GnomAD database, including 21,893 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 0.52 (21893 hom., cov: 31)
• Consequence: ESRRG NM_206594.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206594.3. 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
	ESRRG	NM_001134285.3		c.-106+389T>G		intron	N/A	NP_001127757.1	P62508-2
	ESRRG	NM_001243509.2		c.-105-19500T>G		intron	N/A	NP_001230438.1	P62508-2
	ESRRG	NM_001243510.3		c.-223-19500T>G		intron	N/A	NP_001230439.1	P62508-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRG	ENST00000359162.6	TSL:1	c.-105-19500T>G		intron	N/A	ENSP00000352077.2	P62508-2
	ESRRG	ENST00000366940.6	TSL:1	c.-106+389T>G		intron	N/A	ENSP00000355907.2	P62508-2
	ESRRG	ENST00000493603.5	TSL:1	c.-223-19500T>G		intron	N/A	ENSP00000419594.1	P62508-2

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78221 AN: 151564 Hom.: 21887 Cov.: 31

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.563

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

GnomAD4 genome AF: 0.516 AC: 78243 AN: 151684 Hom.: 21893 Cov.: 31 AF XY: 0.506 AC XY: 37472 AN XY: 74076

African (AFR) AF: 0.333 AC: 13773 AN: 41346

American (AMR) AF: 0.426 AC: 6481 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1273 AN: 5148

South Asian (SAS) AF: 0.554 AC: 2660 AN: 4802

European-Finnish (FIN) AF: 0.534 AC: 5606 AN: 10494

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44148 AN: 67902

Other (OTH) AF: 0.564 AC: 1182 AN: 2094

Alfa AF: 0.564 Hom.: 3715

Bravo AF: 0.495

Asia WGS AF: 0.445 AC: 1551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		-2.3
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: rs1561189; hg19: chr1-217132515;