rs17686866

Variant names:

• chr1-217011923-C-A
• rs17686866
• ENST00000359162.6:c.-105-72250G>T

Variant summary

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

The ENST00000359162.6(ESRRG):​c.-105-72250G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 152,092 control chromosomes in the GnomAD database, including 2,463 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 0.16 (2463 hom., cov: 32)
• Consequence: ESRRG ENST00000359162.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 8 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 (AMR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359162.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRG	NM_001134285.3		c.-229-52238G>T		intron	N/A	NP_001127757.1
	ESRRG	NM_001243509.2		c.-577-11199G>T		intron	N/A	NP_001230438.1
	ESRRG	NM_001243510.3		c.-223-72250G>T		intron	N/A	NP_001230439.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRG	ENST00000359162.6	TSL:1	c.-105-72250G>T		intron	N/A	ENSP00000352077.2
	ESRRG	ENST00000366940.6	TSL:1	c.-229-52238G>T		intron	N/A	ENSP00000355907.2
	ESRRG	ENST00000493603.5	TSL:1	c.-223-72250G>T		intron	N/A	ENSP00000419594.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23953 AN: 151974 Hom.: 2462 Cov.: 32

Gnomad AFR AF: 0.0351

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0741

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.157 AC: 23953 AN: 152092 Hom.: 2463 Cov.: 32 AF XY: 0.164 AC XY: 12200 AN XY: 74324

African (AFR) AF: 0.0350 AC: 1452 AN: 41518

American (AMR) AF: 0.217 AC: 3309 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1062 AN: 5182

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4826

European-Finnish (FIN) AF: 0.320 AC: 3375 AN: 10532

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13418 AN: 67986

Other (OTH) AF: 0.149 AC: 313 AN: 2104

Alfa AF: 0.186 Hom.: 444

Bravo AF: 0.149

Asia WGS AF: 0.115 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.19
DANN	Benign	0.42
PhyloP100		-1.3
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: rs17686866; hg19: chr1-217185265;