rs2347867

chr6-151908715-G-A

Variant summary

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

The NM_000125.4(ESR1):c.760+27944G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,862 control chromosomes in the GnomAD database, including 22,803 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 0.52 (22803 hom., cov: 31)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESR1	NM_000125.4	c.760+27944G>A		intron_variant		ENST00000206249.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESR1	ENST00000206249.8	c.760+27944G>A		intron_variant		1	NM_000125.4	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79414 AN: 151742 Hom.: 22805 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.767

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.523 AC: 79439 AN: 151862 Hom.: 22803 Cov.: 31 AF XY: 0.518 AC XY: 38438 AN XY: 74252

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.743

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.563

Alfa AF: 0.637 Hom.: 51894

Bravo AF: 0.502

Asia WGS AF: 0.315 AC: 1099 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.068
Dann	Benign	0.19

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: rs2347867; hg19: chr6-152229850;