Variant 6-151880740-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000125.4(ESR1):c.729T>C(p.Arg243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 1,609,552 control chromosomes in the GnomAD database, including 746,158 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 0.97 ( 72147 hom., cov: 33)

Exomes 𝑓: 0.96 ( 674011 hom. )

Consequence

ESR1
NM_000125.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.124

Variant links:

Genes affected

ESR1 (HGNC:3467): (estrogen receptor 1) This gene encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by this gene regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by this gene plays a key role in breast cancer, endometrial cancer, and osteoporosis. This gene is reported to have dozens of transcript variants due to the use of alternate promoters and alternative splicing, however, the full-length nature of many of these variants remain uncertain. [provided by RefSeq, Jul 2020]

ESR1 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=-0.53).

BP7

Synonymous conserved (PhyloP=0.124 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_000125.4 linkuse as main transcript	c.729T>C	p.Arg243=	synonymous_variant	3/8	ENST00000206249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000206249.8 linkuse as main transcript	c.729T>C	p.Arg243=	synonymous_variant	3/8	1	NM_000125.4	P1	P03372-1

Frequencies

GnomAD3 genomes

AF:

0.973

AC:

148111

AN:

152238

Hom.:

72087

Cov.:

show subpopulations

Gnomad AFR

AF:

0.994

Gnomad AMI

AF:

0.999

Gnomad AMR

AF:

0.979

Gnomad ASJ

AF:

0.941

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.977

Gnomad FIN

AF:

0.956

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.960

Gnomad OTH

AF:

0.977

GnomAD3 exomes

AF:

0.970

AC:

243858

AN:

251378

Hom.:

118322

AF XY:

0.970

AC XY:

131750

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.994

Gnomad AMR exome

AF:

0.978

Gnomad ASJ exome

AF:

0.940

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.980

Gnomad FIN exome

AF:

0.959

Gnomad NFE exome

AF:

0.962

Gnomad OTH exome

AF:

0.968

GnomAD4 exome

AF:

0.962

AC:

1401412

AN:

1457196

Hom.:

674011

Cov.:

AF XY:

0.962

AC XY:

697957

AN XY:

725372

show subpopulations

Gnomad4 AFR exome

AF:

0.995

Gnomad4 AMR exome

AF:

0.978

Gnomad4 ASJ exome

AF:

0.940

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.977

Gnomad4 FIN exome

AF:

0.960

Gnomad4 NFE exome

AF:

0.958

Gnomad4 OTH exome

AF:

0.965

GnomAD4 genome

AF:

0.973

AC:

148230

AN:

152356

Hom.:

72147

Cov.:

AF XY:

0.973

AC XY:

72440

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.994

Gnomad4 AMR

AF:

0.979

Gnomad4 ASJ

AF:

0.941

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.977

Gnomad4 FIN

AF:

0.956

Gnomad4 NFE

AF:

0.960

Gnomad4 OTH

AF:

0.977

Alfa

AF:

0.963

Hom.:

53886

Bravo

AF:

0.976

Asia WGS

AF:

0.990

AC:

3441

AN:

3478

EpiCase

AF:

0.964

EpiControl

AF:

0.964

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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