Variant 6-151807942-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000125.4(ESR1):c.30T>C(p.Ser10=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,613,166 control chromosomes in the GnomAD database, including 182,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17171 hom., cov: 33)

Exomes 𝑓: 0.47 ( 165449 hom. )

Consequence

ESR1
NM_000125.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.664

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-151807942-T-C is Benign according to our data. Variant chr6-151807942-T-C is described in ClinVar as [Benign]. Clinvar id is 1250979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.664 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.483 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.30T>C	p.Ser10=	synonymous_variant	1/8	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.30T>C	p.Ser10=	synonymous_variant	1/8	1	NM_000125.4	ENSP00000206249	P1	P03372-1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72099

AN:

151918

Hom.:

17166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.469

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.382

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.463

AC:

114483

AN:

247438

Hom.:

26590

AF XY:

0.465

AC XY:

62395

AN XY:

134134

show subpopulations

Gnomad AFR exome

AF:

0.491

Gnomad AMR exome

AF:

0.447

Gnomad ASJ exome

AF:

0.510

Gnomad EAS exome

AF:

0.364

Gnomad SAS exome

AF:

0.493

Gnomad FIN exome

AF:

0.419

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.465

GnomAD4 exome

AF:

0.475

AC:

693862

AN:

1461130

Hom.:

165449

Cov.:

AF XY:

0.475

AC XY:

345476

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.489

Gnomad4 AMR exome

AF:

0.450

Gnomad4 ASJ exome

AF:

0.509

Gnomad4 EAS exome

AF:

0.390

Gnomad4 SAS exome

AF:

0.486

Gnomad4 FIN exome

AF:

0.425

Gnomad4 NFE exome

AF:

0.479

Gnomad4 OTH exome

AF:

0.481

GnomAD4 genome

AF:

0.474

AC:

72129

AN:

152036

Hom.:

17171

Cov.:

AF XY:

0.472

AC XY:

35058

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.489

Gnomad4 AMR

AF:

0.469

Gnomad4 ASJ

AF:

0.511

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.498

Gnomad4 FIN

AF:

0.421

Gnomad4 NFE

AF:

0.480

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.469

Hom.:

24155

Bravo

AF:

0.472

Asia WGS

AF:

0.445

AC:

1548

AN:

3478

EpiCase

AF:

0.477

EpiControl

AF:

0.476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 17, 2018

- -

Familial cancer of breast;C1832662:Myocardial infarction, susceptibility to;C3809250:Estrogen resistance syndrome;C3887485:Migraine with or without aura, susceptibility to, 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.2

DANN

Benign

0.49

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over