rs2504065

Variant names:

• chr6-151774032-G-A
• rs2504065
• ENST00000404742.5:c.-70-33811G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151774032-G-A
• chr6-151774032-G-T

Variant summary

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

The ENST00000404742.5(ESR1):​c.-70-33811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,082 control chromosomes in the GnomAD database, including 17,061 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 0.47 (17061 hom., cov: 32)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 11 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000404742.5. 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_001122742.2		c.-70-33811G>A		intron	N/A	NP_001116214.1
	ESR1	NM_001385568.1		c.-70-33811G>A		intron	N/A	NP_001372497.1
	ESR1	NM_001385570.1		c.-70-33811G>A		intron	N/A	NP_001372499.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000404742.5	TSL:1	c.-70-33811G>A		intron	N/A	ENSP00000385373.1
	ESR1	ENST00000473497.5	TSL:1	n.205-33811G>A		intron	N/A
	ESR1	ENST00000440973.5	TSL:5	c.-70-33811G>A		intron	N/A	ENSP00000405330.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71113 AN: 151964 Hom.: 17065 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.468 AC: 71125 AN: 152082 Hom.: 17061 Cov.: 32 AF XY: 0.475 AC XY: 35309 AN XY: 74326

African (AFR) AF: 0.380 AC: 15768 AN: 41484

American (AMR) AF: 0.424 AC: 6478 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1740 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2447 AN: 5164

South Asian (SAS) AF: 0.462 AC: 2226 AN: 4820

European-Finnish (FIN) AF: 0.680 AC: 7183 AN: 10556

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33770 AN: 67990

Other (OTH) AF: 0.446 AC: 941 AN: 2112

Alfa AF: 0.478 Hom.: 34879

Bravo AF: 0.445

Asia WGS AF: 0.460 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.010
DANN	Benign	0.17
PhyloP100		-0.90
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: rs2504065; hg19: chr6-152095167;