rs3778089

Variant names:

• chr6-152072626-G-A
• rs3778089
• NM_000125.4:c.1369+11502G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-152072626-G-A
• chr6-152072626-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.1369+11502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,022 control chromosomes in the GnomAD database, including 4,414 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 0.21 (4414 hom., cov: 33)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.960
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1369+11502G>A		intron_variant	Intron 6 of 7	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.1369+11502G>A		intron_variant	Intron 6 of 7	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31138 AN: 151902 Hom.: 4403 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.205 AC: 31194 AN: 152022 Hom.: 4414 Cov.: 33 AF XY: 0.207 AC XY: 15362 AN XY: 74298

African (AFR) AF: 0.386 AC: 15992 AN: 41440

American (AMR) AF: 0.109 AC: 1657 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1877 AN: 5166

South Asian (SAS) AF: 0.200 AC: 965 AN: 4822

European-Finnish (FIN) AF: 0.201 AC: 2122 AN: 10562

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7617 AN: 67984

Other (OTH) AF: 0.200 AC: 421 AN: 2104

Alfa AF: 0.133 Hom.: 1457

Bravo AF: 0.205

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.42
PhyloP100		-0.96
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: rs3778089; hg19: chr6-152393761;