rs726283

Positions:

• chr6-151981874-G-A
• chr6-151981874-G-C

Variant summary

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

The NM_000125.4(ESR1):​c.1097-29782G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,060 control chromosomes in the GnomAD database, including 28,660 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 0.57 (28660 hom., cov: 33)
• Consequence: ESR1 NM_000125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_000125.4	c.1097-29782G>A		intron_variant		ENST00000206249.8	NP_000116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000206249.8	c.1097-29782G>A		intron_variant		1	NM_000125.4	ENSP00000206249	P1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86200 AN: 151940 Hom.: 28663 Cov.: 33

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.617

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

GnomAD4 genome AF: 0.567 AC: 86214 AN: 152060 Hom.: 28660 Cov.: 33 AF XY: 0.568 AC XY: 42222 AN XY: 74350

Gnomad4 AFR AF: 0.218

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.729

Gnomad4 OTH AF: 0.611

Alfa AF: 0.645 Hom.: 4289

Bravo AF: 0.552

Asia WGS AF: 0.399 AC: 1393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.028
DANN	Benign	0.78

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: rs726283; hg19: chr6-152303009;