rs10495034

Positions:

• chr1-216724739-C-T

Variant summary

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

The ENST00000359162.6(ESRRG):​c.-13-47248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0613 in 152,090 control chromosomes in the GnomAD database, including 358 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 0.061 (358 hom., cov: 32)
• Consequence: ESRRG ENST00000359162.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.853

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRG	NM_001134285.3	c.-13-47248G>A		intron_variant			NP_001127757.1
ESRRG	NM_001243505.2	c.-165+140322G>A		intron_variant			NP_001230434.1
ESRRG	NM_001243506.2	c.-83-73650G>A		intron_variant			NP_001230435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRG	ENST00000359162.6	c.-13-47248G>A		intron_variant		1		ENSP00000352077
ESRRG	ENST00000360012.7	c.-13-47248G>A		intron_variant		1		ENSP00000353108
ESRRG	ENST00000361395.6	c.-13-47248G>A		intron_variant		1		ENSP00000354584

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9309 AN: 151972 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0677

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0456

Gnomad OTH AF: 0.0602

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

GnomAD4 genome AF: 0.0613 AC: 9324 AN: 152090 Hom.: 358 Cov.: 32 AF XY: 0.0632 AC XY: 4701 AN XY: 74342

Gnomad4 AFR AF: 0.0905

Gnomad4 AMR AF: 0.0392

Gnomad4 ASJ AF: 0.0677

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.0456

Gnomad4 OTH AF: 0.0591

Alfa AF: 0.0500 Hom.: 271

Bravo AF: 0.0588

Asia WGS AF: 0.0190 AC: 66 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.49

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: rs10495034; hg19: chr1-216898081; COSMIC: COSV63153789; COSMIC: COSV63153789;