rs1884052

Variant names:

• chr6-151970231-G-C
• rs1884052
• NM_000125.4:c.1096+25723G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-151970231-G-C
• chr6-151970231-G-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.1096+25723G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.856 in 152,000 control chromosomes in the GnomAD database, including 56,001 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 0.86 (56001 hom., cov: 31)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55
• Publications: 17 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000125.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	NM_000125.4	MANE Select	c.1096+25723G>C		intron	N/A	NP_000116.2
	ESR1	NM_001291230.2		c.1102+25723G>C		intron	N/A	NP_001278159.1
	ESR1	NM_001122740.2		c.1096+25723G>C		intron	N/A	NP_001116212.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000206249.8	TSL:1 MANE Select	c.1096+25723G>C		intron	N/A	ENSP00000206249.3
	ESR1	ENST00000406599.5	TSL:1	c.453-90760G>C		intron	N/A	ENSP00000384064.1
	ESR1	ENST00000427531.6	TSL:1	c.577+25723G>C		intron	N/A	ENSP00000394721.2

Frequencies

GnomAD3 genomes AF: 0.856 AC: 130021 AN: 151882 Hom.: 55973 Cov.: 31

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.864

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.869

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

GnomAD4 genome AF: 0.856 AC: 130105 AN: 152000 Hom.: 56001 Cov.: 31 AF XY: 0.850 AC XY: 63138 AN XY: 74254

African (AFR) AF: 0.916 AC: 38004 AN: 41500

American (AMR) AF: 0.884 AC: 13488 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 2998 AN: 3468

East Asian (EAS) AF: 0.668 AC: 3439 AN: 5152

South Asian (SAS) AF: 0.689 AC: 3312 AN: 4808

European-Finnish (FIN) AF: 0.778 AC: 8180 AN: 10518

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.850 AC: 57785 AN: 67988

Other (OTH) AF: 0.866 AC: 1824 AN: 2106

Alfa AF: 0.861 Hom.: 7015

Bravo AF: 0.868

Asia WGS AF: 0.685 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.020
DANN	Benign	0.35
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1884052; hg19: chr6-152291366;