rs974276

Variant summary

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

The NM_000125.4(ESR1):​c.1369+161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,148 control chromosomes in the GnomAD database, including 5,303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 5303 hom., cov: 33)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0510
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 6-152061285-A-G is Benign according to our data. Variant chr6-152061285-A-G is described in ClinVar as [Benign]. Clinvar id is 1241299.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ESR1NM_000125.4 linkuse as main transcriptc.1369+161A>G intron_variant ENST00000206249.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ESR1ENST00000206249.8 linkuse as main transcriptc.1369+161A>G intron_variant 1 NM_000125.4 P1P03372-1

Frequencies

GnomAD3 genomes
AF:
0.219
AC:
33292
AN:
152030
Hom.:
5293
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.436
Gnomad AMI
AF:
0.130
Gnomad AMR
AF:
0.107
Gnomad ASJ
AF:
0.110
Gnomad EAS
AF:
0.369
Gnomad SAS
AF:
0.233
Gnomad FIN
AF:
0.200
Gnomad MID
AF:
0.111
Gnomad NFE
AF:
0.111
Gnomad OTH
AF:
0.204
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.219
AC:
33339
AN:
152148
Hom.:
5303
Cov.:
33
AF XY:
0.220
AC XY:
16374
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.436
Gnomad4 AMR
AF:
0.106
Gnomad4 ASJ
AF:
0.110
Gnomad4 EAS
AF:
0.369
Gnomad4 SAS
AF:
0.230
Gnomad4 FIN
AF:
0.200
Gnomad4 NFE
AF:
0.111
Gnomad4 OTH
AF:
0.206
Alfa
AF:
0.165
Hom.:
430
Bravo
AF:
0.220
Asia WGS
AF:
0.295
AC:
1024
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 submitterclinical testingGeneDxAug 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
4.4
DANN
Benign
0.35

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.

Other links and lift over

dbSNP: rs974276; hg19: chr6-152382420; COSMIC: COSV52798424; COSMIC: COSV52798424; API