1-216622353-G-A

Variant names:

• chr1-216622353-G-A
• rs11577585
• NM_001438.4:c.589+28620C>T

Variant summary

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

The NM_001438.4(ESRRG):​c.589+28620C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,024 control chromosomes in the GnomAD database, including 2,379 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 0.17 (2379 hom., cov: 32)
• Consequence: ESRRG NM_001438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438.4. 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_001438.4	MANE Select	c.589+28620C>T		intron	N/A	NP_001429.2
	ESRRG	NM_001243518.2		c.604+28620C>T		intron	N/A	NP_001230447.1
	ESRRG	NM_001134285.3		c.520+28620C>T		intron	N/A	NP_001127757.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRG	ENST00000408911.8	TSL:1 MANE Select	c.589+28620C>T		intron	N/A	ENSP00000386171.3
	ESRRG	ENST00000366937.5	TSL:1	c.604+28620C>T		intron	N/A	ENSP00000355904.1
	ESRRG	ENST00000359162.6	TSL:1	c.520+28620C>T		intron	N/A	ENSP00000352077.2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25484 AN: 151906 Hom.: 2376 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.168 AC: 25503 AN: 152024 Hom.: 2379 Cov.: 32 AF XY: 0.164 AC XY: 12184 AN XY: 74318

African (AFR) AF: 0.116 AC: 4802 AN: 41484

American (AMR) AF: 0.141 AC: 2151 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3468

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5178

South Asian (SAS) AF: 0.165 AC: 792 AN: 4808

European-Finnish (FIN) AF: 0.168 AC: 1771 AN: 10550

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14528 AN: 67942

Other (OTH) AF: 0.166 AC: 350 AN: 2112

Alfa AF: 0.200 Hom.: 5524

Bravo AF: 0.162

Asia WGS AF: 0.0980 AC: 344 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	1.0
DANN	Benign	0.57
PhyloP100		-0.64
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: rs11577585; hg19: chr1-216795695;