1-217070040-A-T

Position:

• chr1-217070040-A-T

Variant summary

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

The NM_206594.3(ESRRG):​c.-224+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 NM_206594.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532

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]

ESRRG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRRG	XM_047449307.1	c.-782T>A		5_prime_UTR_variant	1/9		XP_047305263.1
ESRRG	XM_011509266.4	c.-782T>A		5_prime_UTR_variant	1/9		XP_011507568.1
ESRRG	XM_047449344.1	c.-1027T>A		5_prime_UTR_variant	1/13		XP_047305300.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRRG	ENST00000359162.6	c.-106+19467T>A		intron_variant		1		ENSP00000352077.2
ESRRG	ENST00000366940.6	c.-230+67627T>A		intron_variant		1		ENSP00000355907.2
ESRRG	ENST00000493603.5	c.-224+67627T>A		intron_variant		1		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

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.0939

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.176

Alfa AF: 0.0667 Hom.: 84

Bravo AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.64

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: rs7531250; hg19: chr1-217243382;