rs3841686

Variant names:

• chr6-152060952-C-CT
• rs3841686
• NM_000125.4:c.1236-34dupT

Your query was ambiguous. Multiple possible variants found:

• chr6-152060952-C-CT
• chr6-152060952-C-CTTTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000125.4(ESR1):​c.1236-34dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0969 in 1,499,170 control chromosomes in the GnomAD database, including 9,048 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1210 hom., cov: 31)
  • Exomes 𝑓: 0.095 (7838 hom.)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• 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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1236-34dupT		intron_variant	Intron 5 of 7	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.1236-39_1236-38insT		intron_variant	Intron 5 of 7	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17039 AN: 151708 Hom.: 1211 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.119 AC: 18298 AN: 153482 AF XY: 0.122

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.0396

Gnomad ASJ exome AF: 0.0998

Gnomad EAS exome AF: 0.346

Gnomad FIN exome AF: 0.176

Gnomad NFE exome AF: 0.0834

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0952 AC: 128286 AN: 1347344 Hom.: 7838 Cov.: 24 AF XY: 0.0973 AC XY: 64902 AN XY: 666848

African (AFR) AF: 0.125 AC: 3796 AN: 30422

American (AMR) AF: 0.0427 AC: 1520 AN: 35616

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 2442 AN: 24816

East Asian (EAS) AF: 0.314 AC: 11101 AN: 35336

South Asian (SAS) AF: 0.158 AC: 12023 AN: 76210

European-Finnish (FIN) AF: 0.175 AC: 8422 AN: 48188

Middle Eastern (MID) AF: 0.0917 AC: 442 AN: 4822

European-Non Finnish (NFE) AF: 0.0794 AC: 82295 AN: 1035936

Other (OTH) AF: 0.112 AC: 6245 AN: 55998

GnomAD4 genome AF: 0.112 AC: 17050 AN: 151826 Hom.: 1210 Cov.: 31 AF XY: 0.117 AC XY: 8676 AN XY: 74198

African (AFR) AF: 0.130 AC: 5362 AN: 41374

American (AMR) AF: 0.0642 AC: 978 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 365 AN: 3460

East Asian (EAS) AF: 0.336 AC: 1733 AN: 5156

South Asian (SAS) AF: 0.169 AC: 814 AN: 4816

European-Finnish (FIN) AF: 0.178 AC: 1869 AN: 10524

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0822 AC: 5584 AN: 67964

Other (OTH) AF: 0.114 AC: 239 AN: 2102

Alfa AF: 0.0929 Hom.: 122

Bravo AF: 0.103

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.33
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: rs3841686; hg19: chr6-152382087;