rs1415193

Variant names:

• chr6-151771503-T-A
• rs1415193
• ENST00000404742.5:c.-70-36340T>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151771503-T-A
• chr6-151771503-T-G

Variant summary

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

The ENST00000404742.5(ESR1):​c.-70-36340T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,114 control chromosomes in the GnomAD database, including 12,941 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 0.37 (12941 hom., cov: 33)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_001122742.2	c.-70-36340T>A		intron_variant	Intron 2 of 9		NP_001116214.1
ESR1	NM_001385568.1	c.-70-36340T>A		intron_variant	Intron 2 of 9		NP_001372497.1
ESR1	NM_001385570.1	c.-70-36340T>A		intron_variant	Intron 2 of 8		NP_001372499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000404742.5	c.-70-36340T>A		intron_variant	Intron 2 of 2	1		ENSP00000385373.1
ESR1	ENST00000473497.5	n.205-36340T>A		intron_variant	Intron 2 of 2	1
ESR1	ENST00000440973.5	c.-70-36340T>A		intron_variant	Intron 2 of 9	5		ENSP00000405330.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56092 AN: 151996 Hom.: 12950 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.369 AC: 56081 AN: 152114 Hom.: 12941 Cov.: 33 AF XY: 0.369 AC XY: 27411 AN XY: 74366

African (AFR) AF: 0.108 AC: 4500 AN: 41526

American (AMR) AF: 0.395 AC: 6027 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3466

East Asian (EAS) AF: 0.113 AC: 588 AN: 5188

South Asian (SAS) AF: 0.314 AC: 1513 AN: 4812

European-Finnish (FIN) AF: 0.556 AC: 5866 AN: 10558

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34559 AN: 67978

Other (OTH) AF: 0.369 AC: 779 AN: 2112

Alfa AF: 0.443 Hom.: 2095

Bravo AF: 0.343

Asia WGS AF: 0.218 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.2
DANN	Benign	0.66
PhyloP100		0.51
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: rs1415193; hg19: chr6-152092638;