rs10779279

Positions:

• chr1-216752630-G-A

Variant summary

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

The ENST00000359162.6(ESRRG):​c.-13-75139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 152,088 control chromosomes in the GnomAD database, including 450 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 0.069 (450 hom., cov: 32)
• Consequence: ESRRG ENST00000359162.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124904512	XR_007066880.1	n.7102+548C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRRG	ENST00000359162.6	c.-13-75139C>T		intron_variant		1
ESRRG	ENST00000360012.7	c.-14+52313C>T		intron_variant		1
ESRRG	ENST00000361395.6	c.-13-75139C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10567 AN: 151970 Hom.: 450 Cov.: 32

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0868

Gnomad ASJ AF: 0.0866

Gnomad EAS AF: 0.0225

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0875

Gnomad OTH AF: 0.0789

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

GnomAD4 genome AF: 0.0694 AC: 10562 AN: 152088 Hom.: 450 Cov.: 32 AF XY: 0.0718 AC XY: 5338 AN XY: 74338

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0866

Gnomad4 ASJ AF: 0.0866

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.0875

Gnomad4 OTH AF: 0.0795

Alfa AF: 0.0849 Hom.: 751

Bravo AF: 0.0628

Asia WGS AF: 0.0560 AC: 193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.63

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: rs10779279; hg19: chr1-216925972;