rs851991

Variant names:

• chr6-151685446-C-T
• rs851991
• ENST00000473497.5:n.74-16429C>T

Variant summary

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

The NM_001385568.1(ESR1):​c.-201-16429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,926 control chromosomes in the GnomAD database, including 13,776 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 0.42 (13776 hom., cov: 32)
• Consequence: ESR1 NM_001385568.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• 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

ENSG00000294140 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385568.1. 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_001385568.1		c.-201-16429C>T		intron	N/A	NP_001372497.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000473497.5	TSL:1	n.74-16429C>T		intron	N/A
	ESR1	ENST00000947759.1		c.-201-16429C>T		intron	N/A	ENSP00000617818.1
	ENSG00000294140	ENST00000721398.1		n.86-2143C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63411 AN: 151808 Hom.: 13771 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.418 AC: 63457 AN: 151926 Hom.: 13776 Cov.: 32 AF XY: 0.413 AC XY: 30693 AN XY: 74254

African (AFR) AF: 0.348 AC: 14404 AN: 41420

American (AMR) AF: 0.375 AC: 5732 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1882 AN: 3468

East Asian (EAS) AF: 0.115 AC: 592 AN: 5160

South Asian (SAS) AF: 0.431 AC: 2076 AN: 4818

European-Finnish (FIN) AF: 0.494 AC: 5206 AN: 10548

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32135 AN: 67932

Other (OTH) AF: 0.407 AC: 858 AN: 2106

Alfa AF: 0.455 Hom.: 25500

Bravo AF: 0.405

Asia WGS AF: 0.323 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.6
DANN	Benign	0.90
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs851991; hg19: chr6-152006581;