rs2813545

Variant names:

• chr6-152111182-G-C
• rs2813545
• ENST00000427531.6:c.851-14084G>C

Variant summary

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

The NM_001328100.2(ESR1):​c.851-14084G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,084 control chromosomes in the GnomAD database, including 3,884 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 0.22 (3884 hom., cov: 32)
• Consequence: ESR1 NM_001328100.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721
• Publications: 8 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000298278 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001328100.2. 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_001328100.2		c.851-14084G>C		intron	N/A	NP_001315029.1	P03372-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000427531.6	TSL:1	c.851-14084G>C		intron	N/A	ENSP00000394721.2	P03372-4
	ESR1	ENST00000641399.1		n.1071-7081G>C		intron	N/A
	ENSG00000298278	ENST00000754431.1		n.-187C>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34017 AN: 151966 Hom.: 3884 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.224 AC: 34032 AN: 152084 Hom.: 3884 Cov.: 32 AF XY: 0.223 AC XY: 16604 AN XY: 74348

African (AFR) AF: 0.258 AC: 10705 AN: 41466

American (AMR) AF: 0.198 AC: 3025 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3470

East Asian (EAS) AF: 0.126 AC: 652 AN: 5176

South Asian (SAS) AF: 0.134 AC: 646 AN: 4814

European-Finnish (FIN) AF: 0.306 AC: 3241 AN: 10582

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14447 AN: 67974

Other (OTH) AF: 0.206 AC: 435 AN: 2112

Alfa AF: 0.214 Hom.: 450

Bravo AF: 0.220

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.42
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2813545; hg19: chr6-152432317;