rs2818964

Variant names:

• chr1-216509106-G-A
• rs2818964
• NM_001438.4:c.1133-1923C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-216509106-G-A
• chr1-216509106-G-C
• chr1-216509106-G-T

Variant summary

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

The NM_001438.4(ESRRG):​c.1133-1923C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,982 control chromosomes in the GnomAD database, including 24,296 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 0.56 (24296 hom., cov: 32)
• Consequence: ESRRG NM_001438.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001438.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRG	NM_001438.4	MANE Select	c.1133-1923C>T		intron	N/A	NP_001429.2
	ESRRG	NM_001243518.2		c.1169-1923C>T		intron	N/A	NP_001230447.1	P62508-5
	ESRRG	NM_001134285.3		c.1064-1923C>T		intron	N/A	NP_001127757.1	P62508-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESRRG	ENST00000408911.8	TSL:1 MANE Select	c.1133-1923C>T		intron	N/A	ENSP00000386171.3	P62508-1
	ESRRG	ENST00000366937.5	TSL:1	c.1169-1923C>T		intron	N/A	ENSP00000355904.1	P62508-5
	ESRRG	ENST00000359162.6	TSL:1	c.1064-1923C>T		intron	N/A	ENSP00000352077.2	P62508-2

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84719 AN: 151864 Hom.: 24269 Cov.: 32

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.558 AC: 84787 AN: 151982 Hom.: 24296 Cov.: 32 AF XY: 0.550 AC XY: 40855 AN XY: 74302

African (AFR) AF: 0.602 AC: 24960 AN: 41428

American (AMR) AF: 0.415 AC: 6338 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1396 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1247 AN: 5170

South Asian (SAS) AF: 0.411 AC: 1980 AN: 4816

European-Finnish (FIN) AF: 0.611 AC: 6446 AN: 10550

Middle Eastern (MID) AF: 0.431 AC: 125 AN: 290

European-Non Finnish (NFE) AF: 0.600 AC: 40784 AN: 67960

Other (OTH) AF: 0.508 AC: 1072 AN: 2110

Alfa AF: 0.573 Hom.: 20615

Bravo AF: 0.544

Asia WGS AF: 0.374 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.14
DANN	Benign	0.42
PhyloP100		-1.4
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: rs2818964; hg19: chr1-216682448;