rs2504063

Variant names:

• chr6-151769572-A-G
• rs2504063
• ENST00000404742.5:c.-70-38271A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-151769572-A-G
• chr6-151769572-A-T

Variant summary

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

The NM_001122742.2(ESR1):​c.-70-38271A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,932 control chromosomes in the GnomAD database, including 20,140 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 0.50 (20140 hom., cov: 31)
• Consequence: ESR1 NM_001122742.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 41 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122742.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	NM_001122742.2		c.-70-38271A>G		intron	N/A	NP_001116214.1	G4XH65
	ESR1	NM_001385568.1		c.-70-38271A>G		intron	N/A	NP_001372497.1	P03372-1
	ESR1	NM_001385570.1		c.-70-38271A>G		intron	N/A	NP_001372499.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000404742.5	TSL:1	c.-70-38271A>G		intron	N/A	ENSP00000385373.1	Q5T5H8
	ESR1	ENST00000473497.5	TSL:1	n.205-38271A>G		intron	N/A
	ESR1	ENST00000440973.5	TSL:5	c.-70-38271A>G		intron	N/A	ENSP00000405330.1	P03372-1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76132 AN: 151814 Hom.: 20145 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.501 AC: 76136 AN: 151932 Hom.: 20140 Cov.: 31 AF XY: 0.503 AC XY: 37348 AN XY: 74246

African (AFR) AF: 0.367 AC: 15178 AN: 41402

American (AMR) AF: 0.463 AC: 7076 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2046 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1060 AN: 5156

South Asian (SAS) AF: 0.419 AC: 2016 AN: 4808

European-Finnish (FIN) AF: 0.679 AC: 7163 AN: 10550

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39947 AN: 67970

Other (OTH) AF: 0.477 AC: 1004 AN: 2106

Alfa AF: 0.547 Hom.: 109584

Bravo AF: 0.478

Asia WGS AF: 0.319 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.72
PhyloP100		-0.10
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: rs2504063; hg19: chr6-152090707; COSMIC: COSV68604392;