rs9383939

Variant names:

• chr6-151685043-G-A
• rs9383939
• ENST00000473497.5:n.74-16832G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-151685043-G-A
• chr6-151685043-G-C

Variant summary

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

The ENST00000473497.5(ESR1):​n.74-16832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 150,772 control chromosomes in the GnomAD database, including 926 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 0.095 (926 hom., cov: 31)
• Consequence: ESR1 ENST00000473497.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• 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

ENSG00000294140 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR1	NM_001385568.1	c.-201-16832G>A		intron_variant	Intron 1 of 9		NP_001372497.1
ESR1	XM_017010377.2	c.-201-16832G>A		intron_variant	Intron 2 of 10		XP_016865866.1
ESR1	XM_017010380.2	c.-71+28280G>A		intron_variant	Intron 1 of 8		XP_016865869.1
ESR1	XM_047418290.1	c.-201-16832G>A		intron_variant	Intron 1 of 9		XP_047274246.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000473497.5	n.74-16832G>A		intron_variant	Intron 1 of 2	1
ENSG00000294140	ENST00000721398.1	n.86-2546G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14326 AN: 150708 Hom.: 926 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0616

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.0937

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.0682

Gnomad NFE AF: 0.0680

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0950 AC: 14330 AN: 150772 Hom.: 926 Cov.: 31 AF XY: 0.0939 AC XY: 6905 AN XY: 73568

African (AFR) AF: 0.135 AC: 5529 AN: 41032

American (AMR) AF: 0.0737 AC: 1117 AN: 15164

Ashkenazi Jewish (ASJ) AF: 0.0616 AC: 213 AN: 3460

East Asian (EAS) AF: 0.370 AC: 1895 AN: 5116

South Asian (SAS) AF: 0.0934 AC: 445 AN: 4764

European-Finnish (FIN) AF: 0.0256 AC: 261 AN: 10186

Middle Eastern (MID) AF: 0.0669 AC: 19 AN: 284

European-Non Finnish (NFE) AF: 0.0680 AC: 4609 AN: 67780

Other (OTH) AF: 0.105 AC: 218 AN: 2076

Alfa AF: 0.0711 Hom.: 739

Bravo AF: 0.101

Asia WGS AF: 0.217 AC: 751 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		0.063

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9383939; hg19: chr6-152006178;