6-151719156-T-C

Variant names:

• chr6-151719156-T-C
• rs12525163
• ENST00000404742.5:c.-71+17151T>C

Variant summary

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

The NM_001122742.2(ESR1):​c.-71+17151T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,128 control chromosomes in the GnomAD database, including 5,450 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 0.26 (5450 hom., cov: 32)
• Consequence: ESR1 NM_001122742.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.914
• Publications: 27 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

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 (NFE) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122742.2. 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_001122742.2		c.-71+17151T>C		intron	N/A	NP_001116214.1	G4XH65
	ESR1	NM_001385568.1		c.-71+17151T>C		intron	N/A	NP_001372497.1	P03372-1
	ESR1	NM_001385570.1		c.-71+17151T>C		intron	N/A	NP_001372499.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000404742.5	TSL:1	c.-71+17151T>C		intron	N/A	ENSP00000385373.1	Q5T5H8
	ESR1	ENST00000473497.5	TSL:1	n.204+17151T>C		intron	N/A
	ESR1	ENST00000440973.5	TSL:5	c.-71+17151T>C		intron	N/A	ENSP00000405330.1	P03372-1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39904 AN: 152010 Hom.: 5443 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.263 AC: 39939 AN: 152128 Hom.: 5450 Cov.: 32 AF XY: 0.261 AC XY: 19421 AN XY: 74372

African (AFR) AF: 0.260 AC: 10795 AN: 41520

American (AMR) AF: 0.253 AC: 3875 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 657 AN: 3464

East Asian (EAS) AF: 0.162 AC: 836 AN: 5176

South Asian (SAS) AF: 0.154 AC: 740 AN: 4816

European-Finnish (FIN) AF: 0.338 AC: 3572 AN: 10572

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18695 AN: 67976

Other (OTH) AF: 0.226 AC: 476 AN: 2108

Alfa AF: 0.262 Hom.: 16755

Bravo AF: 0.258

Asia WGS AF: 0.167 AC: 584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.050
DANN	Benign	0.57
PhyloP100		-0.91
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: rs12525163; hg19: chr6-152040291;