rs1062577

chr6-152102770-T-Achr6-152102770-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000125.4(ESR1):c.*3804T>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 0.101 in 216,682 control chromosomes in the GnomAD database, including 1,473 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 0.094 (823 hom., cov: 32)
  • Exomes 𝑓: 0.12 (650 hom.)
• Consequence: ESR1 NM_000125.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.782

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_000125.4	c.*3804T>A		3_prime_UTR_variant	8/8	ENST00000206249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000206249.8	c.*3804T>A		3_prime_UTR_variant	8/8	1	NM_000125.4	P1

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 14267 AN: 151988 Hom.: 819 Cov.: 32

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0776

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0695

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.117 AC: 7528 AN: 64574 Hom.: 650 Cov.: 0 AF XY: 0.118 AC XY: 3529 AN XY: 30024

Gnomad4 AFR exome AF: 0.0866

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.0849

Gnomad4 EAS exome AF: 0.294

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0795

Gnomad4 OTH exome AF: 0.0993

GnomAD4 genome AF: 0.0940 AC: 14295 AN: 152108 Hom.: 823 Cov.: 32 AF XY: 0.0965 AC XY: 7179 AN XY: 74372

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.0776

Gnomad4 NFE AF: 0.0695

Gnomad4 OTH AF: 0.120

Alfa AF: 0.0243 Hom.: 20

Bravo AF: 0.0978

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	7.6
Dann	Benign	0.83

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: rs1062577; hg19: chr6-152423905; COSMIC: COSV52802680; COSMIC: COSV52802680;