1-217064844-C-T

Variant names:

• chr1-217064844-C-T
• rs4537652
• ENST00000359162.6:c.-106+24663G>A

Variant summary

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

The NM_206594.3(ESRRG):​c.-224+24663G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,968 control chromosomes in the GnomAD database, including 11,312 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 0.37 (11312 hom., cov: 32)
• Consequence: ESRRG NM_206594.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.369
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.677 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.-230+72823G>A		intron	N/A	NP_001127757.1	P62508-2
	ESRRG	NM_001243509.2		c.-578+12008G>A		intron	N/A	NP_001230438.1	P62508-2
	ESRRG	NM_001243510.3		c.-224+72823G>A		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.-106+24663G>A		intron	N/A	ENSP00000352077.2	P62508-2
	ESRRG	ENST00000366940.6	TSL:1	c.-230+72823G>A		intron	N/A	ENSP00000355907.2	P62508-2
	ESRRG	ENST00000493603.5	TSL:1	c.-224+72823G>A		intron	N/A	ENSP00000419594.1	P62508-2

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56564 AN: 151852 Hom.: 11295 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.373 AC: 56628 AN: 151968 Hom.: 11312 Cov.: 32 AF XY: 0.371 AC XY: 27523 AN XY: 74274

African (AFR) AF: 0.267 AC: 11088 AN: 41466

American (AMR) AF: 0.333 AC: 5082 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3466

East Asian (EAS) AF: 0.696 AC: 3596 AN: 5170

South Asian (SAS) AF: 0.351 AC: 1689 AN: 4818

European-Finnish (FIN) AF: 0.395 AC: 4158 AN: 10528

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28329 AN: 67950

Other (OTH) AF: 0.353 AC: 743 AN: 2106

Alfa AF: 0.404 Hom.: 34136

Bravo AF: 0.367

Asia WGS AF: 0.452 AC: 1568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.37
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: rs4537652; hg19: chr1-217238186;