6-151808173-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000125.4(ESR1):c.261G>C(p.Ala87Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0791 in 1,584,942 control chromosomes in the GnomAD database, including 5,621 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.069 ( 492 hom., cov: 33)

Exomes 𝑓: 0.080 ( 5129 hom. )

Consequence

ESR1
NM_000125.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.103

Publications

40 publications found

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 Gene-Disease associations (from GenCC):

estrogen resistance syndrome
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ESR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 6-151808173-G-C is Benign according to our data. Variant chr6-151808173-G-C is described in ClinVar as [Benign]. Clinvar id is 1180284.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.103 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4 link	c.261G>C	p.Ala87Ala	synonymous_variant	Exon 1 of 8	ENST00000206249.8	NP_000116.2	P03372-1G4XH65

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8 link	c.261G>C	p.Ala87Ala	synonymous_variant	Exon 1 of 8	1	NM_000125.4	ENSP00000206249.3		P03372-1

Frequencies

GnomAD3 genomes

AF:

0.0688

AC:

10464

AN:

152112

Hom.:

492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0392

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0331

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.0370

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0920

Gnomad OTH

AF:

0.0559

GnomAD2 exomes

AF:

0.0659

AC:

12699

AN:

192798

AF XY:

0.0656

show subpopulations

Gnomad AFR exome

AF:

0.0389

Gnomad AMR exome

AF:

0.0275

Gnomad ASJ exome

AF:

0.0699

Gnomad EAS exome

AF:

0.000552

Gnomad FIN exome

AF:

0.129

Gnomad NFE exome

AF:

0.0910

Gnomad OTH exome

AF:

0.0671

GnomAD4 exome

AF:

0.0802

AC:

114906

AN:

1432710

Hom.:

5129

Cov.:

AF XY:

0.0790

AC XY:

56071

AN XY:

709686

show subpopulations

African (AFR)

AF:

0.0357

AC:

1174

AN:

32916

American (AMR)

AF:

0.0284

AC:

1157

AN:

40754

Ashkenazi Jewish (ASJ)

AF:

0.0675

AC:

1721

AN:

25494

East Asian (EAS)

AF:

0.000235

AC:

AN:

38240

South Asian (SAS)

AF:

0.0349

AC:

2884

AN:

82572

European-Finnish (FIN)

AF:

0.129

AC:

6459

AN:

50140

Middle Eastern (MID)

AF:

0.0284

AC:

162

AN:

5702

European-Non Finnish (NFE)

AF:

0.0884

AC:

97021

AN:

1097682

Other (OTH)

AF:

0.0729

AC:

4319

AN:

59210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

6473

12946

19420

25893

32366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0688

AC:

10467

AN:

152232

Hom.:

492

Cov.:

AF XY:

0.0692

AC XY:

5153

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0391

AC:

1626

AN:

41572

American (AMR)

AF:

0.0331

AC:

507

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3470

East Asian (EAS)

AF:

0.000583

AC:

AN:

5146

South Asian (SAS)

AF:

0.0373

AC:

180

AN:

4830

European-Finnish (FIN)

AF:

0.134

AC:

1426

AN:

10604

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0920

AC:

6253

AN:

67982

Other (OTH)

AF:

0.0553

AC:

117

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

514

1028

1542

2056

2570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0729

Hom.:

163

Bravo

AF:

0.0591

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ESR1-related disorder

Benign:1

May 31, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Oct 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26585143, 28815558, 24607813) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.4

(source)

DANN

Benign

0.66

PhyloP100

-0.10

PromoterAI

-0.0046

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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6-151808173-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over