1-216757671-C-G

Position:

• chr1-216757671-C-G

Variant summary

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

The ENST00000359162.6(ESRRG):​c.-13-80180G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,930 control chromosomes in the GnomAD database, including 43,147 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 0.74 (43147 hom., cov: 31)
• Consequence: ESRRG ENST00000359162.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89

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]

LOC124904512 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904512	XR_007066880.1	n.2609G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRG	ENST00000359162.6	c.-13-80180G>C		intron_variant		1		ENSP00000352077
ESRRG	ENST00000360012.7	c.-14+47272G>C		intron_variant		1		ENSP00000353108
ESRRG	ENST00000361395.6	c.-13-80180G>C		intron_variant		1		ENSP00000354584

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113081 AN: 151812 Hom.: 43095 Cov.: 31

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.745

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.745 AC: 113183 AN: 151930 Hom.: 43147 Cov.: 31 AF XY: 0.743 AC XY: 55175 AN XY: 74226

Gnomad4 AFR AF: 0.892

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.745

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.700

Gnomad4 OTH AF: 0.746

Alfa AF: 0.712 Hom.: 4585

Bravo AF: 0.746

Asia WGS AF: 0.700 AC: 2433 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	12
DANN	Benign	0.71

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: rs1416615; hg19: chr1-216931013; COSMIC: COSV63153926;