Variant chr6-152061190-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000125.4(ESR1):c.1369+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,487,136 control chromosomes in the GnomAD database, including 9,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.11 ( 1210 hom., cov: 32)

Exomes 𝑓: 0.099 ( 8335 hom. )

Consequence

ESR1
NM_000125.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.83

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-152061190-A-G is Benign according to our data. Variant chr6-152061190-A-G is described in ClinVar as [Benign]. Clinvar id is 1248080.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 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.1369+66A>G		intron_variant		ENST00000206249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000206249.8 linkuse as main transcript	c.1369+66A>G		intron_variant		1	NM_000125.4	P1	P03372-1

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17063

AN:

152032

Hom.:

1211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.0649

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.334

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0821

Gnomad OTH

AF:

0.112

GnomAD4 exome

AF:

0.0990

AC:

132165

AN:

1334986

Hom.:

8335

AF XY:

0.101

AC XY:

67880

AN XY:

671280

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.0406

Gnomad4 ASJ exome

AF:

0.100

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.175

Gnomad4 NFE exome

AF:

0.0822

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.112

AC:

17074

AN:

152150

Hom.:

1210

Cov.:

AF XY:

0.117

AC XY:

8698

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.0647

Gnomad4 ASJ

AF:

0.105

Gnomad4 EAS

AF:

0.334

Gnomad4 SAS

AF:

0.170

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.0822

Gnomad4 OTH

AF:

0.113

Alfa

AF:

0.0879

Hom.:

1149

Bravo

AF:

0.103

Asia WGS

AF:

0.236

AC:

820

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.6

DANN

Benign

0.56

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