rs3798577

Positions:

• chr6-152099995-T-C
• chr6-152099995-T-G

Variant summary

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

The ENST00000206249.8(ESR1):​c.*1029T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 398,584 control chromosomes in the GnomAD database, including 41,644 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 0.45 (15622 hom., cov: 33)
  • Exomes 𝑓: 0.46 (26022 hom.)
• Consequence: ESR1 ENST00000206249.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_000125.4	c.*1029T>C		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.*1029T>C		3_prime_UTR_variant	8/8	1	NM_000125.4	ENSP00000206249	P1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68935 AN: 151978 Hom.: 15623 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.458 AC: 112769 AN: 246488 Hom.: 26022 Cov.: 0 AF XY: 0.458 AC XY: 57250 AN XY: 124940

Gnomad4 AFR exome AF: 0.431

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.453 AC: 68972 AN: 152096 Hom.: 15622 Cov.: 33 AF XY: 0.454 AC XY: 33773 AN XY: 74354

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.455

Alfa AF: 0.468 Hom.: 16316

Bravo AF: 0.454

Asia WGS AF: 0.479 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.66
DANN	Benign	0.80

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: rs3798577; hg19: chr6-152421130; COSMIC: COSV52805170; COSMIC: COSV52805170;