Genetic Variant ESRRG:p.Ser319Ser (chr1-216519327-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001438.4(ESRRG):c.957G>A(p.Ser319Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,612,634 control chromosomes in the GnomAD database, including 157,727 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 0.51 ( 21315 hom., cov: 32)

Exomes 𝑓: 0.42 ( 136412 hom. )

Consequence

ESRRG
NM_001438.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.15

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP7

Synonymous conserved (PhyloP=-1.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRG	NM_001438.4 link	c.957G>A	p.Ser319Ser	synonymous_variant	Exon 6 of 7	ENST00000408911.8	NP_001429.2	P62508-1F1D8R5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRG	ENST00000408911.8 link	c.957G>A	p.Ser319Ser	synonymous_variant	Exon 6 of 7	1	NM_001438.4	ENSP00000386171.3		P62508-1

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78131

AN:

151920

Hom.:

21288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.516

Gnomad AMR

AF:

0.611

Gnomad ASJ

AF:

0.594

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.584

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.541

GnomAD3 exomes

AF:

0.506

AC:

126803

AN:

250762

Hom.:

34093

AF XY:

0.500

AC XY:

67757

AN XY:

135516

show subpopulations

Gnomad AFR exome

AF:

0.672

Gnomad AMR exome

AF:

0.638

Gnomad ASJ exome

AF:

0.600

Gnomad EAS exome

AF:

0.721

Gnomad SAS exome

AF:

0.584

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.498

GnomAD4 exome

AF:

0.419

AC:

612391

AN:

1460596

Hom.:

136412

Cov.:

AF XY:

0.424

AC XY:

308051

AN XY:

726644

show subpopulations

Gnomad4 AFR exome

AF:

0.682

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.603

Gnomad4 EAS exome

AF:

0.700

Gnomad4 SAS exome

AF:

0.582

Gnomad4 FIN exome

AF:

0.390

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.474

GnomAD4 genome

AF:

0.514

AC:

78206

AN:

152038

Hom.:

21315

Cov.:

AF XY:

0.519

AC XY:

38542

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.665

Gnomad4 AMR

AF:

0.611

Gnomad4 ASJ

AF:

0.594

Gnomad4 EAS

AF:

0.720

Gnomad4 SAS

AF:

0.585

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.394

Gnomad4 OTH

AF:

0.538

Alfa

AF:

0.434

Hom.:

18916

Bravo

AF:

0.538

Asia WGS

AF:

0.622

AC:

2164

AN:

3478

EpiCase

AF:

0.428

EpiControl

AF:

0.426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.3

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over