rs3020390

Variant names:

• chr6-151955323-A-G
• rs3020390
• NM_000125.4:c.1096+10815A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-151955323-A-G
• chr6-151955323-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.1096+10815A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 152,078 control chromosomes in the GnomAD database, including 24,702 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 0.55 (24702 hom., cov: 32)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1096+10815A>G		intron_variant	Intron 4 of 7	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.1096+10815A>G		intron_variant	Intron 4 of 7	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 83044 AN: 151958 Hom.: 24703 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.546 AC: 83066 AN: 152078 Hom.: 24702 Cov.: 32 AF XY: 0.543 AC XY: 40324 AN XY: 74316

African (AFR) AF: 0.319 AC: 13247 AN: 41498

American (AMR) AF: 0.545 AC: 8332 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2279 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1924 AN: 5172

South Asian (SAS) AF: 0.429 AC: 2066 AN: 4818

European-Finnish (FIN) AF: 0.665 AC: 7026 AN: 10560

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46118 AN: 67962

Other (OTH) AF: 0.576 AC: 1217 AN: 2112

Alfa AF: 0.632 Hom.: 6488

Bravo AF: 0.524

Asia WGS AF: 0.396 AC: 1378 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.024
DANN	Benign	0.50
PhyloP100		-0.36
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: rs3020390; hg19: chr6-152276458;