ENST00000359162.6:c.-13-80180G>C

Variant names:

• chr1-216757671-C-G
• rs1416615
• ENST00000359162.6:c.-13-80180G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

LOC124904512 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LOC124904512	XR_007066880.1	n.2609G>C		non_coding_transcript_exon_variant	Exon 1 of 2
ESRRG	NM_001134285.3	c.-13-80180G>C		intron_variant	Intron 3 of 8		NP_001127757.1
ESRRG	NM_001243509.2	c.-13-80180G>C		intron_variant	Intron 3 of 8		NP_001230438.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRG	ENST00000359162.6	c.-13-80180G>C		intron_variant	Intron 2 of 7	1		ENSP00000352077.2
ESRRG	ENST00000360012.7	c.-14+47272G>C		intron_variant	Intron 1 of 6	1		ENSP00000353108.3
ESRRG	ENST00000361395.6	c.-13-80180G>C		intron_variant	Intron 2 of 7	1		ENSP00000354584.2

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

African (AFR) AF: 0.892 AC: 37016 AN: 41494

American (AMR) AF: 0.653 AC: 9941 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.745 AC: 2582 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2360 AN: 5118

South Asian (SAS) AF: 0.854 AC: 4110 AN: 4814

European-Finnish (FIN) AF: 0.677 AC: 7157 AN: 10570

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47518 AN: 67914

Other (OTH) AF: 0.746 AC: 1578 AN: 2114

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
PhyloP100		2.9
Mutation Taster		=99/1	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: rs1416615; hg19: chr1-216931013; COSMIC: COSV63153926;