chr1-216618263-A-G

Position:

• chr1-216618263-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001438.4(ESRRG):​c.589+32710T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,116 control chromosomes in the GnomAD database, including 13,901 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 0.42 (13901 hom., cov: 33)
• Consequence: ESRRG NM_001438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRG	NM_001438.4	c.589+32710T>C		intron_variant		ENST00000408911.8	NP_001429.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRG	ENST00000408911.8	c.589+32710T>C		intron_variant		1	NM_001438.4	ENSP00000386171	P1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63148 AN: 151998 Hom.: 13886 Cov.: 33

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.415 AC: 63196 AN: 152116 Hom.: 13901 Cov.: 33 AF XY: 0.408 AC XY: 30371 AN XY: 74348

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.409

Alfa AF: 0.477 Hom.: 32557

Bravo AF: 0.399

Asia WGS AF: 0.261 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs1857407; hg19: chr1-216791605;