rs11155820

Variant names:

• chr6-151883075-A-G
• rs11155820
• NM_000125.4:c.760+2304A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-151883075-A-G
• chr6-151883075-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000125.4(ESR1):​c.760+2304A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,994 control chromosomes in the GnomAD database, including 4,656 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 (4656 hom., cov: 31)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 19 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.760+2304A>G		intron_variant	Intron 3 of 7	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.760+2304A>G		intron_variant	Intron 3 of 7	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33664 AN: 151884 Hom.: 4658 Cov.: 31

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.0367

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.221 AC: 33665 AN: 151994 Hom.: 4656 Cov.: 31 AF XY: 0.219 AC XY: 16302 AN XY: 74276

African (AFR) AF: 0.0601 AC: 2492 AN: 41492

American (AMR) AF: 0.243 AC: 3711 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1278 AN: 3468

East Asian (EAS) AF: 0.0366 AC: 188 AN: 5134

South Asian (SAS) AF: 0.265 AC: 1272 AN: 4804

European-Finnish (FIN) AF: 0.257 AC: 2712 AN: 10534

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.310 AC: 21053 AN: 67968

Other (OTH) AF: 0.238 AC: 504 AN: 2116

Alfa AF: 0.281 Hom.: 23152

Bravo AF: 0.212

Asia WGS AF: 0.154 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.35
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11155820; hg19: chr6-152204210;