rs9341070

Positions:

• chr6-152099062-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000125.4(ESR1):​c.*96C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 930,322 control chromosomes in the GnomAD database, including 7 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 0.0017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (6 hom.)
• Consequence: ESR1 NM_000125.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.451

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_000125.4	c.*96C>T		3_prime_UTR_variant	8/8	ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.*96C>T		3_prime_UTR_variant	8/8	1	NM_000125.4	ENSP00000206249	P1

Frequencies

GnomAD3 genomes AF: 0.00175 AC: 266 AN: 152172 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00278

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.00212 AC: 1646 AN: 778032 Hom.: 6 Cov.: 10 AF XY: 0.00213 AC XY: 860 AN XY: 404640

Gnomad4 AFR exome AF: 0.000493

Gnomad4 AMR exome AF: 0.00165

Gnomad4 ASJ exome AF: 0.00146

Gnomad4 EAS exome AF: 0.000209

Gnomad4 SAS exome AF: 0.000629

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.00250

Gnomad4 OTH exome AF: 0.00277

GnomAD4 genome AF: 0.00175 AC: 266 AN: 152290 Hom.: 1 Cov.: 32 AF XY: 0.00161 AC XY: 120 AN XY: 74460

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00278

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00226 Hom.: 0

Bravo AF: 0.00178

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs9341070; hg19: chr6-152420197;