Variant 6-151944387-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000206249.8(ESR1):c.975G>C(p.Pro325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 1,613,900 control chromosomes in the GnomAD database, including 464,431 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 0.79 ( 47934 hom., cov: 31)

Exomes 𝑓: 0.75 ( 416497 hom. )

Consequence

ESR1
ENST00000206249.8 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

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=-0.93).

BP7

Synonymous conserved (PhyloP=-1.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.89 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_000125.4 linkuse as main transcript	c.975G>C	p.Pro325=	synonymous_variant	4/8	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8 linkuse as main transcript	c.975G>C	p.Pro325=	synonymous_variant	4/8	1	NM_000125.4	ENSP00000206249	P1	P03372-1

Frequencies

GnomAD3 genomes

AF:

0.789

AC:

119880

AN:

151994

Hom.:

47896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.897

Gnomad AMI

AF:

0.852

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.798

Gnomad EAS

AF:

0.498

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.725

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.777

Gnomad OTH

AF:

0.795

GnomAD3 exomes

AF:

0.730

AC:

183513

AN:

251348

Hom.:

68388

AF XY:

0.726

AC XY:

98605

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.901

Gnomad AMR exome

AF:

0.692

Gnomad ASJ exome

AF:

0.794

Gnomad EAS exome

AF:

0.508

Gnomad SAS exome

AF:

0.606

Gnomad FIN exome

AF:

0.736

Gnomad NFE exome

AF:

0.779

Gnomad OTH exome

AF:

0.747

GnomAD4 exome

AF:

0.752

AC:

1098715

AN:

1461788

Hom.:

416497

Cov.:

AF XY:

0.748

AC XY:

543763

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.907

Gnomad4 AMR exome

AF:

0.696

Gnomad4 ASJ exome

AF:

0.801

Gnomad4 EAS exome

AF:

0.501

Gnomad4 SAS exome

AF:

0.607

Gnomad4 FIN exome

AF:

0.736

Gnomad4 NFE exome

AF:

0.769

Gnomad4 OTH exome

AF:

0.746

GnomAD4 genome

AF:

0.789

AC:

119972

AN:

152112

Hom.:

47934

Cov.:

AF XY:

0.780

AC XY:

57999

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.897

Gnomad4 AMR

AF:

0.744

Gnomad4 ASJ

AF:

0.798

Gnomad4 EAS

AF:

0.497

Gnomad4 SAS

AF:

0.592

Gnomad4 FIN

AF:

0.725

Gnomad4 NFE

AF:

0.777

Gnomad4 OTH

AF:

0.791

Alfa

AF:

0.774

Hom.:

11902

Bravo

AF:

0.796

Asia WGS

AF:

0.584

AC:

2035

AN:

3478

EpiCase

AF:

0.777

EpiControl

AF:

0.773

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.2

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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