rs2504065

Positions:

• chr6-151774032-G-A
• chr6-151774032-G-T

Variant summary

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

The NM_001122742.2(ESR1):​c.-70-33811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,082 control chromosomes in the GnomAD database, including 17,061 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 0.47 (17061 hom., cov: 32)
• Consequence: ESR1 NM_001122742.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900

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]

ESR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR1	NM_001122742.2	c.-70-33811G>A		intron_variant			NP_001116214.1
ESR1	NM_001385568.1	c.-70-33811G>A		intron_variant			NP_001372497.1
ESR1	NM_001385570.1	c.-70-33811G>A		intron_variant			NP_001372499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR1	ENST00000404742.5	c.-70-33811G>A		intron_variant		1		ENSP00000385373.1
ESR1	ENST00000473497.5	n.205-33811G>A		intron_variant		1
ESR1	ENST00000440973.5	c.-70-33811G>A		intron_variant		5		ENSP00000405330.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71113 AN: 151964 Hom.: 17065 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.680

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.447

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

GnomAD4 genome AF: 0.468 AC: 71125 AN: 152082 Hom.: 17061 Cov.: 32 AF XY: 0.475 AC XY: 35309 AN XY: 74326

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.680

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.446

Alfa AF: 0.482 Hom.: 25566

Bravo AF: 0.445

Asia WGS AF: 0.460 AC: 1602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.010
DANN	Benign	0.17

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: rs2504065; hg19: chr6-152095167;