6-152100719-C-A

Position:

• chr6-152100719-C-A

Variant summary

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

The NM_000125.4(ESR1):​c.*1753C>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 0.077 in 222,140 control chromosomes in the GnomAD database, including 1,196 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 0.077 (683 hom., cov: 31)
  • Exomes 𝑓: 0.078 (513 hom.)
• Consequence: ESR1 NM_000125.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_000125.4	c.*1753C>A		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.*1753C>A		3_prime_UTR_variant	8/8	1	NM_000125.4	ENSP00000206249.3

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11415 AN: 149482 Hom.: 673 Cov.: 31

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.0763

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0376

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0427

Gnomad MID AF: 0.0355

Gnomad NFE AF: 0.0314

Gnomad OTH AF: 0.0748

GnomAD4 exome AF: 0.0777 AC: 5636 AN: 72552 Hom.: 513 Cov.: 0 AF XY: 0.0779 AC XY: 2609 AN XY: 33508

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.122

Gnomad4 ASJ exome AF: 0.0344

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.0414

Gnomad4 NFE exome AF: 0.0332

Gnomad4 OTH exome AF: 0.0618

GnomAD4 genome AF: 0.0767 AC: 11470 AN: 149588 Hom.: 683 Cov.: 31 AF XY: 0.0801 AC XY: 5825 AN XY: 72728

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0376

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.0427

Gnomad4 NFE AF: 0.0314

Gnomad4 OTH AF: 0.0768

Alfa AF: 0.0434 Hom.: 205

Bravo AF: 0.0820

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.93
DANN	Benign	0.63

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: rs3798758; hg19: chr6-152421854;