rs2377360

Variant names:

• chr1-217027541-G-A
• rs2377360
• ENST00000359162.6:c.-106+61966C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-217027541-G-A
• chr1-217027541-G-C

Variant summary

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

The ENST00000359162.6(ESRRG):​c.-106+61966C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,928 control chromosomes in the GnomAD database, including 33,594 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 0.65 (33594 hom., cov: 31)
• Consequence: ESRRG ENST00000359162.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 10 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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 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.-229-67856C>T		intron	N/A	NP_001127757.1
	ESRRG	NM_001243509.2		c.-577-26817C>T		intron	N/A	NP_001230438.1
	ESRRG	NM_001243510.3		c.-223-87868C>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.-106+61966C>T		intron	N/A	ENSP00000352077.2
	ESRRG	ENST00000366940.6	TSL:1	c.-229-67856C>T		intron	N/A	ENSP00000355907.2
	ESRRG	ENST00000493603.5	TSL:1	c.-223-87868C>T		intron	N/A	ENSP00000419594.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98445 AN: 151808 Hom.: 33592 Cov.: 31

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.648 AC: 98477 AN: 151928 Hom.: 33594 Cov.: 31 AF XY: 0.647 AC XY: 48020 AN XY: 74252

African (AFR) AF: 0.428 AC: 17724 AN: 41394

American (AMR) AF: 0.598 AC: 9117 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2334 AN: 3464

East Asian (EAS) AF: 0.818 AC: 4221 AN: 5160

South Asian (SAS) AF: 0.667 AC: 3216 AN: 4822

European-Finnish (FIN) AF: 0.773 AC: 8150 AN: 10550

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51393 AN: 67970

Other (OTH) AF: 0.651 AC: 1373 AN: 2110

Alfa AF: 0.680 Hom.: 45753

Bravo AF: 0.626

Asia WGS AF: 0.698 AC: 2426 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		1.7
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: rs2377360; hg19: chr1-217200883;