rs6930355

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000125.4(ESR1):​c.1236-10735T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,138 control chromosomes in the GnomAD database, including 5,371 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 0.22 ( 5371 hom., cov: 32)

Consequence

ESR1
NM_000125.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ESR1NM_000125.4 linkuse as main transcriptc.1236-10735T>C intron_variant ENST00000206249.8 NP_000116.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ESR1ENST00000206249.8 linkuse as main transcriptc.1236-10735T>C intron_variant 1 NM_000125.4 ENSP00000206249 P1P03372-1

Frequencies

GnomAD3 genomes
AF:
0.220
AC:
33492
AN:
152020
Hom.:
5365
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.440
Gnomad AMI
AF:
0.130
Gnomad AMR
AF:
0.107
Gnomad ASJ
AF:
0.110
Gnomad EAS
AF:
0.369
Gnomad SAS
AF:
0.232
Gnomad FIN
AF:
0.200
Gnomad MID
AF:
0.111
Gnomad NFE
AF:
0.111
Gnomad OTH
AF:
0.207
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.220
AC:
33533
AN:
152138
Hom.:
5371
Cov.:
32
AF XY:
0.221
AC XY:
16468
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.441
Gnomad4 AMR
AF:
0.107
Gnomad4 ASJ
AF:
0.110
Gnomad4 EAS
AF:
0.369
Gnomad4 SAS
AF:
0.229
Gnomad4 FIN
AF:
0.200
Gnomad4 NFE
AF:
0.111
Gnomad4 OTH
AF:
0.209
Alfa
AF:
0.157
Hom.:
470
Bravo
AF:
0.222
Asia WGS
AF:
0.294
AC:
1019
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
7.6
DANN
Benign
0.64

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: rs6930355; hg19: chr6-152371391; API