chr1-217070040-A-T

Variant names:

• chr1-217070040-A-T
• rs7531250
• ENST00000359162.6:c.-106+19467T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359162.6(ESRRG):​c.-106+19467T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,100 control chromosomes in the GnomAD database, including 1,987 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 0.16 (1987 hom., cov: 31)
• Consequence: ESRRG ENST00000359162.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359162.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRG	NM_001134285.3		c.-230+67627T>A		intron	N/A	NP_001127757.1
	ESRRG	NM_001243509.2		c.-578+6812T>A		intron	N/A	NP_001230438.1
	ESRRG	NM_001243510.3		c.-224+67627T>A		intron	N/A	NP_001230439.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRG	ENST00000359162.6	TSL:1	c.-106+19467T>A		intron	N/A	ENSP00000352077.2
	ESRRG	ENST00000366940.6	TSL:1	c.-230+67627T>A		intron	N/A	ENSP00000355907.2
	ESRRG	ENST00000493603.5	TSL:1	c.-224+67627T>A		intron	N/A	ENSP00000419594.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24206 AN: 151980 Hom.: 1990 Cov.: 31

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0939

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.159 AC: 24202 AN: 152100 Hom.: 1987 Cov.: 31 AF XY: 0.157 AC XY: 11697 AN XY: 74368

African (AFR) AF: 0.165 AC: 6844 AN: 41478

American (AMR) AF: 0.148 AC: 2260 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3472

East Asian (EAS) AF: 0.0859 AC: 443 AN: 5160

South Asian (SAS) AF: 0.254 AC: 1224 AN: 4818

European-Finnish (FIN) AF: 0.0939 AC: 995 AN: 10598

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11359 AN: 67976

Other (OTH) AF: 0.176 AC: 372 AN: 2108

Alfa AF: 0.0667 Hom.: 84

Bravo AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.64
PhyloP100		0.53
Mutation Taster		=100/0	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: rs7531250; hg19: chr1-217243382;