rs2982552

Variant names:

• chr6-151738428-G-A
• rs2982552
• ENST00000404742.5:c.-71+36423G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151738428-G-A
• chr6-151738428-G-C
• chr6-151738428-G-T

Variant summary

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

The ENST00000404742.5(ESR1):​c.-71+36423G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,940 control chromosomes in the GnomAD database, including 16,819 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 0.45 (16819 hom., cov: 32)
• Consequence: ESR1 ENST00000404742.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.141
• Publications: 25 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_001122742.2	c.-71+36423G>A		intron_variant	Intron 2 of 9		NP_001116214.1
ESR1	NM_001385568.1	c.-71+36423G>A		intron_variant	Intron 2 of 9		NP_001372497.1
ESR1	NM_001385570.1	c.-71+36423G>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.-71+36423G>A		intron_variant	Intron 2 of 2	1		ENSP00000385373.1
ESR1	ENST00000473497.5	n.204+36423G>A		intron_variant	Intron 2 of 2	1
ESR1	ENST00000440973.5	c.-71+36423G>A		intron_variant	Intron 2 of 9	5		ENSP00000405330.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67640 AN: 151822 Hom.: 16820 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.445 AC: 67651 AN: 151940 Hom.: 16819 Cov.: 32 AF XY: 0.449 AC XY: 33350 AN XY: 74254

African (AFR) AF: 0.244 AC: 10090 AN: 41410

American (AMR) AF: 0.463 AC: 7069 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1901 AN: 3466

East Asian (EAS) AF: 0.169 AC: 871 AN: 5164

South Asian (SAS) AF: 0.396 AC: 1900 AN: 4802

European-Finnish (FIN) AF: 0.663 AC: 7003 AN: 10562

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37245 AN: 67962

Other (OTH) AF: 0.422 AC: 891 AN: 2112

Alfa AF: 0.502 Hom.: 78144

Bravo AF: 0.417

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.3
DANN	Benign	0.47
PhyloP100		0.14
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: rs2982552; hg19: chr6-152059563;