rs3798758

Variant names:

• chr6-152100719-C-A
• rs3798758
• NM_000125.4:c.*1753C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-152100719-C-A
• chr6-152100719-C-G
• chr6-152100719-C-T

Variant summary

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

The NM_000125.4(ESR1):​c.*1753C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.077 in 222,140 control chromosomes in the GnomAD database, including 1,196 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 0.077 (683 hom., cov: 31)
  • Exomes 𝑓: 0.078 (513 hom.)
• Consequence: ESR1 NM_000125.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 26 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000125.4. 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_000125.4	MANE Select	c.*1753C>A		3_prime_UTR	Exon 8 of 8	NP_000116.2	P03372-1
	ESR1	NM_001291230.2		c.*1753C>A		3_prime_UTR	Exon 9 of 9	NP_001278159.1
	ESR1	NM_001122740.2		c.*1753C>A		3_prime_UTR	Exon 9 of 9	NP_001116212.1	P03372-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR1	ENST00000206249.8	TSL:1 MANE Select	c.*1753C>A		3_prime_UTR	Exon 8 of 8	ENSP00000206249.3	P03372-1
	ESR1	ENST00000427531.6	TSL:1	c.851-24547C>A		intron	N/A	ENSP00000394721.2	P03372-4
	ESR1	ENST00000440973.5	TSL:5	c.*1753C>A		3_prime_UTR	Exon 10 of 10	ENSP00000405330.1	P03372-1

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11415 AN: 149482 Hom.: 673 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0763

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0376

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0355

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.0748

GnomAD4 exome AF: 0.0777 AC: 5636 AN: 72552 Hom.: 513 Cov.: 0 AF XY: 0.0779 AC XY: 2609 AN XY: 33508

African (AFR) AF: 0.122 AC: 422 AN: 3464

American (AMR) AF: 0.122 AC: 264 AN: 2172

Ashkenazi Jewish (ASJ) AF: 0.0344 AC: 158 AN: 4588

East Asian (EAS) AF: 0.274 AC: 2822 AN: 10296

South Asian (SAS) AF: 0.127 AC: 78 AN: 616

European-Finnish (FIN) AF: 0.0414 AC: 11 AN: 266

Middle Eastern (MID) AF: 0.0543 AC: 24 AN: 442

European-Non Finnish (NFE) AF: 0.0332 AC: 1482 AN: 44640

Other (OTH) AF: 0.0618 AC: 375 AN: 6068

GnomAD4 genome AF: 0.0767 AC: 11470 AN: 149588 Hom.: 683 Cov.: 31 AF XY: 0.0801 AC XY: 5825 AN XY: 72728

African (AFR) AF: 0.124 AC: 5028 AN: 40544

American (AMR) AF: 0.105 AC: 1579 AN: 15010

Ashkenazi Jewish (ASJ) AF: 0.0376 AC: 130 AN: 3456

East Asian (EAS) AF: 0.253 AC: 1292 AN: 5100

South Asian (SAS) AF: 0.140 AC: 660 AN: 4716

European-Finnish (FIN) AF: 0.0427 AC: 419 AN: 9806

Middle Eastern (MID) AF: 0.0345 AC: 10 AN: 290

European-Non Finnish (NFE) AF: 0.0314 AC: 2123 AN: 67680

Other (OTH) AF: 0.0768 AC: 160 AN: 2082

Alfa AF: 0.0510 Hom.: 452

Bravo AF: 0.0820

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.93
DANN	Benign	0.63
PhyloP100		-0.53
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: rs3798758; hg19: chr6-152421854;